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Key value for chemical safety assessment

Effects on fertility

Description of key information

In oral reproduction toxicity studies on mice and rats no adverse effects on reproductive performance were observed and the NOAEL were established to be 3060 and 2200 mg/kg bw/d, respectively.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
3 060 mg/kg bw/day
Study duration:
subacute
Species:
mouse
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

NTP (1990) reported a reproduction and fertility assessment. Diethylene glycol was administered via the drinking water to mice. The male and female mice were given concentrations of 0, 0.35, 1.75 and 3.5 % (= 0, 612, 3063 and 6125 mg/kg bw/day) 7 days before, during and 21 days after a 98-day cohabitation stage. In this experiment, diethylene glycol did not produce changes in the male or female reproductive capability. The NOAEL was found to be 3060 mg/kg bw/day.

Wegener (1953) reported the effect on the reproductive capacity. Male and female rats were given orally (gavage) a daily dose of approx. 2200 mg/kg bw/day over a study duration of 12 weeks. At the dose used in this study, there was nothing to suggest impairment of reproduction or any embryotoxic action of DEG. The NOAEL was found to be 2200 mg/kg bw/day.

Effects on developmental toxicity

Description of key information

In the key study with rabbits, the test item caused up to and including a dose of 1000 mg/kg bw/day no signs of maternal toxicity and no signs of embryo-/fetotoxicity; especially no teratogenic effects could be detected.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

BASF (1989) reported a prenatal toxicity study in rabbits with oral administration (gavage). The oral administration of diethylene glycol to pregnant Himalayan rabbits by stomach tube on day 7 through day 19 p.i. (= post insemination) in dosages of 100, 400 and 1000 mg/kg body weight/day led to no adverse effects which can be causally related to the test substance administration in both the does and in the fetuses. The observable differences between the control group and the substance-treated groups appeared either without a clear dose-response relationship and/or were assessed as being without biological relevance, because the relevant values/findings are to be found in a similar range within the historical control data. The NOAELs for maternal toxicity, embryotoxicity and fetotoxicity were found to be 1000 mg/kg bw/day.

Bushy Run Research Center (1992) reported a developmental toxicity study in rats with oral administration (gavage). Exposure of 1.0, 4.0 and 8.0 mL/kg bw/day from gestation days 6 - 15 resulted in evidence of severe maternal toxicity, including death and kidney injury, at the highest dose group and less severe maternal effects at the 4 mL-dose group. Developmental toxicity as evidenced by reduced fetal weight and delayed ossification was observed at 8.0 mL/kg bw/day. Minimal developmental toxicity was observed at 4 mL/kg bw/day. The NOELs for maternal and developmental toxicity were 1.0 mL/kg bw/day. There was no evidence of teratogenic effects at any dosage.

In another study, timed-pregnant CD-1 mice and CD rats were dosed daily by gavage with undiluted DEG over GD 6-15 (Ballantyne and Snellings, 2005). Mice received 0 (distilled water), 0.6, 2.8, 11.2 g/kg bw/d, and rats 0, 1.1, 4.5, 8.9 g/kg bw/d. Animals were examined daily and at necropsy (GD 18) for gross pathology, maternal body and organ weights, gravid uterus and implant status, foetal weight, sex, and morphological development.

With mice, maternal toxicity was present at 2.8 g/kg bw/d (increased water consumption) and at 11.2 g/kg bw/d (mortality 6/30 mice, increased water consumption). Implantations were comparable across all groups. Foetal body weights were significantly reduced at 11.2 g/kg bw/d without increases in variations or malformations, either total, by category or individually.

With rats, maternal toxicity was present at 4.5 g/kg bw/d (increased water consumption) and at 8.9 g/kg bw/d (mortality 3/25 rats, reduced body weight and food consumption, increased water consumption, kidney and liver weights, and renal histopathology). There were no treatment-related effects on corpora lutea or implantations. Foetal body weights were reduced at 8.9 g/kg bw/d. There were no significant effects with respect to total or individual external or visceral variations. Individual skeletal variations were significantly increased at 8.9 g/kg bw/d (poorly ossified interparietal, thoracic centra number 10 and 13, and bilobed thoracic centrum number 10) and at 4.5 g/kg bw/d (split anterior arch of atlas and bilobed thoracic centrum number 10), which are consistent with reduced foetal body weight. No malformations were observed at any dose groups. Thus, under the conditions of this study, the NOAEL was 0.6 g/kg bw/d with the mouse and 1.1 g/kg bw/d with the rat for maternal toxicity, and 2.8 g/kg bw/d with the mouse and 1.1 g/kg bw/d with the rat for developmental toxicity.

In a developmental toxicity study, DEG was administered by gavage to timed-pregnant Swiss CD-1 mice (26-31/dose) on gestational days (GD) 6-15 at dose levels of 0, 1.25, 5, 10 g/kg bw/d (NTP, PB91 -159327, 1991). Animals were examined daily and at necropsy (GD 17) for maternal body and organ weights, implant status, foetal weight, sex, and morphological development. Food and water consumption and body weights were determined on GD 0, 3, 6, 9, 12, 15, and 17. Maternal body weights did not differ significantly at any doses. At ≥ 5 g/kg bw/d, relative water intake was significantly increased over control for every interval starting at GD 6. Necropsy on GD 17 showed significantly increased absolute and relative kidney weights. At 10 g/kg bw/d, relative food consumption was significantly decreased from GD 6 to 12. Necropsy and histopathologic examination of one high dose animal in extremis on GD 10 revealed evidence of DEG-related renal degeneration and morbidity. Renal tubular degeneration was found in 3/28 of the pregnant high dose females versus 0/20 of the pregnant control females. No effects of DEG were observed on pre- or post-implantation loss. The mean foetal body weight on GD 17 decreased linearly (99%, 96%, and 85% of the control from low to high dose) with a statistical significance seen at the high dose. Examination of the foetuses for external, visceral and skeletal malformations did not reveal any significant effects between dose groups. The 5 g/kg bw/d DEG dose produced significant maternal toxicity, but no clear evidence of developmental toxicity. Hence, the developmental NOAEL was considered to be 5 g/kg bw/d.

Justification for classification or non-classification

The test substance does not affect the reproductive performance and fertility, and neither possesses an embryo/fetotoxic nor a teratogenic potential. Therefore,no classification is warranted according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Additional information