Substance-Specific Issues

Xylene Isomers; classification with respect to embryotoxicity

Substances:

ortho-Xylene; CAS # 95-47-6
meta-Xylene; CAS # 108-38-3
para-Xylene; CAS # 106-42-3

Issue:

Do the xylene isomers fall within the WHMIS D2A criteria for embryotoxicity specified in section 53 of the Controlled Products Regulations (CPR)?

Background:

Xylene [mixed stream, CAS 1330-20-7] which consists of the 3 xylene isomers as well as ethylbenzene falls within the CPR criteria for embryotoxicity (see "Substance-specific Regulatory Issues; Classification of Xylene (mixed stream) with respect to Embryotoxicity").

Consideration:

The CPR criteria encompass products which cause injuries to the embryo and fetus that may occur under conditions that would have no effect on the pregnant female.

Para-xylene (CAS 106-42-3): Fetotoxic effects were observed in rats in the absence of maternal toxicity [1]. In addition, two studies, although they did not meet the CPR criteria as maternal toxicity was reported, could be used to support the evidence of developmental toxicity [2, 4]. Other International Agencies consider p-xylene as producing fetotoxic effects. The International Chemical Safety Cards, (produced by WHO, IPCS and ILO, and endorsed by NIOSH), states "animal tests show that this substance possibly causes toxic effects upon human reproduction".

Ortho-xylene (CAS 95-47-6): Fetotoxic effects were observed in rats and mice in the presence of maternal toxicity [1, 2].

Meta-xylene (CAS 108-38-3): Fetotoxic effects were observed in rabbits in the absence of maternal toxicity [2]. However, there were some limitations or deficiencies in the study, e.g., only one dose was used. Therefore, a dose response could not be observed. Other species were tested but fetotoxic effects were observed either in the presence of maternal toxicity [1] or without maternal toxicity being discussed [2]. In another study, exposure to m-xylene did not affect any of the fetal parameters measured in mice at a dose that did not induce maternal toxicity [3].

Conclusions:

Para-xylene, CAS 106-42-3, falls within the embryotoxicity criteria specified in section 53 of the CPR. Ortho-xylene (CAS 95-47-6) and meta-xylene (CAS 108-38-8) do not meet the criteria specified in CPR 53.

References:

1. Ungvary, G., et al, Studies on the embryotoxic effects of ortho-, meta- and para-xylene, Toxicology, 18 (1980), 61-74.
   
   
2. Ungvary, G., Tatrai, E., On the embryotoxic effects of benzene and its alkyl derivatives in mice, rats and rabbits, Archives of Toxicology, Supplement 8, (1985) 425-430.
   
   
3. Seidenberg J.M. et al, Validation on an In Vivo Developmental Toxicity Screen in the Mouse, Teratogenesis, Carcinogenesis, and Mutagenesis, 6 (1986), 361-374.
   
   
4. Ungvary, G., et al, Study on the role of maternal sex steroid production and metabolism in the embryotoxicity of para-xylene, Toxicology, 19 (1981) 263-268.