Registration Dossier

Administrative data

Description of key information

ALL DATA IN RATS, NOAELs in mg/kg/day
Oral, 90 day: 400
Dermal, 21 days: 1000
Dermal, 90 day: 4000

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
400 mg/kg bw/day

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
4 000 mg/kg bw/day

Additional information

In a guideline (OECD 408) and GLP study, exposure to triethylene glycol methyl ether (TEGME) in the drinking water of rats for 90 days resulted in decreases in mean food consumption, body weight, and body weight gain for males and females in the 4 g/kg/day treatment group and trends for decreased food consumption and body weight for males in the 1.2 g/kg/day treatment group. Water consumption tended to be decreased at each measurement period for females in the 4 g/kg/day treatment group. Small decreases in mean food consumption, body weight, and body weight gain were also apparent for females in the 1.2 g/kg/day treatment group. One female animal from the 4 g/kg/day treatment group died on study Day 37 without apparent cause. Dose-related increases in mean liver weight were observed for male animals in all three TEGME treatment groups. Associated microscopic changes included hepatocellular cytoplasmic vacuolization and/or hepatocellular hypertrophy, for males in the 4 g/kg/day treatment group. Vacuolization or hypertrophy (minimal or mild severity) were also observed in the livers of some males in the 0.4 g/kg/day and 1.2 g/kg/day treatment groups and females in the 4 g/kg/day treatment group. Hypertrophy can be considered a physiological adaptation due to large subchronic doses of the test material, which is likely to be metabolized by alcohol dehydrogenase and aldehyde oxidase in the liver. Treatment-related degeneration and/or atrophy of seminiferous tubules were observed for most males in the 4 g/kg/day treatment group. The cell types affected in the tubules were spermatocytes and developing spermatids. Similar lesions were not observed for males in the 0.4 g/kg/day or 1.2 g/kg/day treatment groups. On the basis of these findings 1200 mg/kg bw/day is considered to be a subchronic LOAEL for TGME and 400mg/kg bw/day a NOAEL under the conditions of this study.

 

In a guideline and GLP study, dermal exposure to TEGME (>10% of total body surface area, shaved, occluded) at doses up to 4000 mg/kg bw/day for 6 hours/day, 5 days/week (except holidays) for 13 weeks produced no clearly-defined indications of systemic toxicity, even with additional emphasis on lymphoid, hematopoietic and reproductive organs. Parameters evaluated included in-life clinical observations, dermal irritation, body weights, feed consumption, hematology, clinical chemistry, urinalysis, estrous cyclicity, selected organ weights, gross pathology and histopathology. The only treatment-related effects noted in this study consisted of focal areas (<2 mm) of dermal irritation in nearly all animals administered TEGME. The dermal irritation was considered secondary to small abrasions induced by repeated clipping of the fur. Areas of the skin that were not abraded by clipping were unaffected by treatment with TEGME. All dermal observations noted during the course of the study were not evident at necropsy. Moreover, microscopic examination of tissue from the dermal test site did not indicate pathologic changes. Based on these findings, 4000 mg/kg bw/day is considered a subchronic dermal NOEL for TEGME systemic toxicity.

No repeat dose toxicity information by the inhalation route is available. Because of the very low volatility of this substance and the low toxicity demonstrated by other routes, it can be concluded that toxicity by the inhalation route is not of concern.

Justification for classification or non-classification

No adverse effects are seen below the thresholds for classification.