Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented, according to accepted guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
1992 guideline was followed, and reliability scoring based on 2001 guideline for Test No. 420
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Hexylene glycol
- Physical state: liquid
- Lot/Batch No.: ST95/507
- Analytical purity: 99.72%
- Expiry date: stable for one year; no expiry date was provided
- Storage condition of test material: room temperature in an unlit cabinet

Test animals

Species:
rat
Strain:
other: Crl:CD. BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate
- Age at study initiation: 5 to 7 weeks old
- Weight at study initiation: Males - 173 to 191 g and Females - 145 to 175 g
- Fasting period before study: Yes, for 19 hours
- Housing: up to 5 rats/sex/cage in suspended stainless steel mesh cages
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1 from Special Diet Services Ltd. was available ad libitum
- Water (e.g. ad libitum): mains water available ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 40 to 70
- Air changes (per hr): up to 15
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not reported
- Amount of vehicle (if gavage): individual dose volumes were calculated from the fasting body weights of the rats on the morning of dosing and the selected dose volume was 10 mL/kg body weight.


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 rats/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Clinical signs were recorded on day 1 and regularly for the remainder of the study (twice daily on days 2,3,4 and once daily from the 5th to the last day). Body weights were recorded prior to dosing, day of dosing, on day 8, and day 15
- Necropsy of survivors performed: yes
- Other examinations performed: gross necropsy was performed with a detailed external and internal examination

- A sighting study was undertaken to allow selection of the discriminating dose level for the main study. The discriminating dose level is the highest of 4 dose levels (5, 50, 500, or 2000 mg/kg body weight) that is non-lethal in the main study. The preliminary investigation was conducted using a group of 2 fasted female rats dosed at 500 mg/kg body weight.
Statistics:
No information provided

Results and discussion

Preliminary study:
Neither of the 2 fasted rats died. Clinical signs included pilo-erection in one rat 3 to 4 hours after dosing. Body weight gains were recorded for both animals during the 14-day observation period. Macroscopic examination at necropsy on day 15 revealed slight distension and darkening of the uterus of one rat.
Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Mortality:
No premature deaths occured
Clinical signs:
Clinical signs apparent in all rats from 2 to 3 hours after dosing included ataxia, decreased activity, muscular flaccidity, and palpebral closure. Pilo-erection and dark feces were seen 4 hours after dosing. Animals recovered by day 2. See attached file 1 (table 3) for further details on clinical signs.
Body weight:
All rats achieved body weight gains during the first and second weeks of the study.
Gross pathology:
Renal pelvic dilatation in one female and a red and distended cecum in another female was observed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Executive summary:

An acute oral toxicity study on hexylene glycol has been performed in accordance with OECD Guidelines for the Testing of Chemicals No. 420 and in compliance with GLP (Gardner, 1996). A sighting study was undertaken to allow selection of the discriminating dose level for the main study. The preliminary investigation was conducted in 2 fasted female rats dosed at 500 mg/kg body weight. Neither of the 2 fasted rats died. Clinical signs included pilo-erection in one rat 3 to 4 hours after dosing. Macroscopic examination at necropsy on day 15 revealed slight distension and darkening of the uterus of one rat. Since no mortality was observed in the sighting study, 5 male and 5 female fasted Crl:CD BR rats were orally administered 2000 mg/kg body weight of hexylene glycol in water (vehicle) by gavage in a volume of 10 mL/kg body weight in the main study. Animals were observed over a 15-day period. No deaths occurred. Clinical signs were apparent in all rats from 2 to 3 hours after dosing and included ataxia, decreased activity, muscular flaccidity, and palpebral closure. Pilo-erection and dark feces also were observed 4 hours after dosing. Animals recovered by day 2. In addition, all rats achieved body weight gains during the first and second weeks of the study. Macroscopic examination at necropsy on day 15 revealed renal pelvic dilatation in one female and a red and distended cecum in another female. Based on the results and under the conditions of the study, the discriminating dose of hexylene glycol in rats was determined to be 2000 mg/kg body weight and the oral LD50 greater than 2000 mg/kg body weight.