Summary of public comments received on the draft screening assessment report for ethylene glycol ethers

Comments on the draft screening assessment report for Ethylene Glycol Ethers (EGEs) to be addressed as part of the Chemicals Management Plan (CMP) were provided by the Canadian Consumer Specialty Products Association, the Glycol Ethers Panel of the American Chemistry Council (ACC), the Ethylene Glycols Panel of the ACC, and the Learning Disabilities Association of Canada.

A summary of comments and responses is included below, organized by topic.

Data and information updates

Summarized comment Summarized response
According to the Chemical Economics Handbook, 157,000 metric tonnes of diethylene glycol (DEG) and 10,000 to 15,000 metric tonnes of triethylene glycol (TEG) were produced in Canada in 2013.  This information could not be validated by the submitter or by other means. Therefore the screening assessment was based on information received from stakeholder’s responses to mandatory Section 71 surveys. These surveys gather information on CMP substances imported and produced in Canada.
According to the International Agency for Research on Cancer (IARC), there is no significant evidence that Ethylene Glycol Butyl Ether Acetate (EGBEA) causes cancer in humans. Consider adding a note to that effect in the risk characterization section. The outcome of the IARC assessment was added to the Health Effects section in the SAR.
Weil (1949) and Spencer (1940) are not appropriate references for the health effects assessments for the following reasons: they are out of date; they provide limited methodology information; and they have documentation issues. The assessment should cite the newer references that were provided.  The 32-day study using DEG (Weil, 1949) will remain in the review. However, based on submitted information, the no-observed-adverse-effect-level (NOAEL) is revised to 850 mg/kg bw/day.
The NOAEL and the lowest-observed-adverse-effect level (LOAEL) reported in the 14-day oral study using TEG is incorrect, and increased urine volume is not an adverse effect. Reference the broadly accepted study NOAEL of 5,916 mg/kg bw/day rather than the one for 1,132 mg/kg bw/day. The screening assessment was revised.
Section 7.2.2 describes the same study (Nolen et al. 1995; EC 2000) twice. The screening assessment was revised.
The screening assessment report incorrectly characterizes the study protocol of Healing et al. (2016) as a 28-day drinking water study. It is a 28- to 32-day gavage study. The screening assessment was revised.
Remove a sentence in Section 7.3.1, which states that animal data can be used to determine DEG levels that protect human health in an acute effects scenario. Under the Global Harmonized System (GHS), DEG has an acute oral toxicity level of Category 4, based on human findings. Also animals are less sensitive than humans to effects of metabolized DEG. Minor changes to clarify the risk characterization for acute exposures were made in the screening assessment. However, a robust critical effect level for acute toxicity in humans could not be determined for DEG.

Correct the year for the Smyth et al. reference in Section 7.1.2 of the assessment; it should be 1944.

The screening assessment was revised.

Methodology

Summarized comment Summarized response
The Government of Canada generated a balanced scientific evaluation, which included a weight of evidence risk-based approach, and a margin of exposure analysis. Stakeholders support the use of an external peer review group and external consultation for the human health section of the screening assessment report. Noted.
The results of the in vivo chromosomal study (UCC, 1987) are questioned. An unpublished study conducted a new analysis with data presented in a mouse genotoxicity study and concluded that the chromosomal effects are not statistically significant.  Although there was a change in the conclusion for a mouse genotoxicity study, the screening assessment was not revised because the significance was uncertain for results from a TEG genotoxicity study conducted on rats.
Evaluate the neurotoxicity of diethylene glycol monobutyl ether (DEGBE) and diethylene glycol n-butyl ether acetate (DGBA). For example, a study by Beyrouty et al. (1993) shows neurotoxic effects of EGEs. An updated literature search for DEGBE did not identify any concerns related to neurotoxicity. This was confirmed in the observed effects cited in Beyrouty et al. (1993). The screening assessment was updated with this information.
Evaluate a clinical study conducted by Beranger et al. (2017) that assessed prenatal exposures to EGEs and incorporate the findings into the screening assessment report. The screening assessment was revised.
Re-evaluate the US EPA assessment of EGBE because it includes a benchmark dose that provides guidance for continuous inhalation. The screening assessment already considered metabolism of EGBE as cited in the US EPA assessment. However, this was not included in the human health risk characterization because effects in humans from EGBE exposures are different than those for experimental animals.
Re-evaluate the TEG no-observed-adverse-effect concentration (NOAEC) of 517 mg/m3 from the 9-day inhalation study because the data for decreases in body weight gains are not statistically significant at 1,036 mg/m3 The screening assessment was revised.
Re-evaluate the Ballantyne and Snellings (2007) sub-chronic study. An increase in urine volume is not considered adverse: it reflects the chemistry and metabolism of EGs. Also slightly increased relative kidney weights are not considered adverse because no changes were observed in the kidney tissues. The screening assessment was revised to show that changes in these parameters are not considered adverse.

Uses and releases

Summarized comment Summarized response
For clarification, DEG is used as an intermediate in the production of polyurethane, antifreeze and polyester. DEG and /or TEG are used in the production of natural gas processing. TEG is also used as a solvent in various industrial applications. The screening assessment was revised.
Rephrase the term “several epidemiology studies” to “clinical case reports of DEG misuses” to provide an accurate description of these uses. The screening assessment was revised to accurately describe the unintentional and unsupported uses of DEG.
Consider incorporating additional uses into Table 5-1 to reflect uses listed in the exposure section. Table 5-1 only contains information specific to data obtained from surveys conducted under the Canadian Environmental Protection Act. Other uses specific to the exposure characterization are included in Section 5. 

Cumulative health risks

Summarized comment Summarized response
Evaluate aggregate and cumulative exposures to EGEs, which show common adverse health effects, such as developmental effects and liver effects. Aggregate exposure to EGEs was not assessed because there is no evidence of co-exposure (i.e. an individual using more than one product containing EGEs in the same day). Cumulative exposure was not assessed because evidence of different forms of EGEs sharing a common mode of action is insufficient.

Occupational exposure

Summarized comment Summarized response
Given the limited chronic and developmental neurotoxicity data, recommend requiring greater margins of safety for the assessed substances, especially for occupational exposures for women of childbearing age. Occupational exposures are not covered because CMP screening assessments evaluate risks of exposure among general populations in Canada rather than risks of exposures in workplaces. However, hazard information from occupational settings is considered in the assessment when it is available and relevant to the general public. CMP risk assessment outcomes that relate to occupational exposure are shared with appropriate occupational health and safety representatives.

Conclusion

Summarized comment Summarized response
Scientific evidence in the draft screening assessment supports the conclusions on diethylene glycol monoethyl ether (DEGEE), EGBEA, and DEGBE. Noted.
The DEG, TEG, and TTEG conclusion is supported. Many comments were provided to improve the draft screening assessment report. Noted.

Risk management

Summarized comment Summarized response
Consider adding EGEs to the Cosmetics Hot List, where relevant. DEG is already on Health Canada’s Cosmetic Ingredient Hotlist, and Significant New Activity (SNAc) provisions under CEPA 1999 for monoglyme are being proposed. Application of the SNAc provisions require any proposed new manufacture, import, or use of the substance be subject to further assessment to determine if the new activity requires risk management.
Assistance is offered to develop a new process to address potential new use patterns for substances assessed during the third phase of the CMP. Noted.

Public consultation and stakeholder engagement

Summarized comment Summarized response
Assistance is offered should additional information be required. Consultation with stakeholders is an essential part of the risk management process. The Government of Canada consults extensively with all affected stakeholders when developing risk management measures.
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