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Description of key information

HG is of low acute toxicity following oral and dermal exposures. Reported oral LD0 values for HG were greater than 2000 mg/kg body weight in rats for both routes of administration. Detailed information on the acute inhalation toxicity of HG is not available. However, the results reported in a reliable investigation have indicated that exposure of male rats to a vapour of HG did not result in deaths within a 8-hour exposure time.

Acute Toxicity: Oral

Acute oral toxicity studies on hexylene glycol (HG), one of which was performed according to test guidelines, have demonstrated that the compound is of low acute toxicity following oral exposure to rats. The studies conducted (described below) all report on LD0 values of greater than 2000 mg/kg body weight for HG.
An acute oral toxicity study on HG has been performed in accordance with OECD Guidelines for the Testing of Chemicals No. 420 and in compliance with GLP (, 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 HG 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 oral LD0 was greater than 2000 mg/kg body weight.
The results of a study conducted by Smyth et al. (1948) support the low acute oral toxicity of HG reported by(1996). In their investigation, Smyth et al. (1948) determined the LD50 of HG in male Sherman rats to be 4700 mg/kg body weight as assessed following oral gavage administration of a range of HG doses (reported as 10, 1, 0.1, etc. g/kg body weight).

Acute Toxicity: Dermal

Acute dermal toxicity studies on HG, one of which was performed according to test guidelines, have demonstrated that the compound is of low acute toxicity following dermal exposure to rats. The dermal LD0 of HG is greater than 2000 mg/kg body weight in rats, and also has been determined to be 13.3 mL/kg body weight in this species. In addition, no clinical signs of systemic toxicity or skin irritation or other dermal reactions were observed in rats.
An acute dermal toxicity study on HG has been performed in accordance with OECD Guidelines for the Testing of Chemicals No. 402 and in compliance with GLP (, 1996). The study was performed in Crl: CD BR rats in which 5 male and 5 female animals were dermally administered 2000 mg/kg body weight of HG in a volume of 2.22 mL/kg body weight. The test substance was applied to the dorsal area (10% of total body surface) under semi-occlusive conditions for an exposure period of 24 hours. Animals were observed over a 15-day period. There were no irritation reactions or other dermal changes at the sites of HG application. In addition, no deaths occurred and no clinical signs of systemic toxicity were observed. A small loss in weight loss was observed in one female on day 15, but no other effects on body weight were observed. Gross pathology revealed renal pelvic dilatation in 2 rats and an enlarged spleen in one other animal. The dermal LD0 of HG was determined to be greater than 2000 mg/kg body weight in rats.
The results of a study conducted by Smythet al. (1948) support the low acute dermal toxicity of HG reported by(1996). In their investigation, Smyth et al. (1948) determined the dermal LD50 of HG in male rabbits to be 13.3 mL/kg body weight as assessed following dermal administration with the use of a rubber cuff.

Acute Toxicity: Inhalation

Acute inhalation toxicity studies that follow current test guidelines have not been performed, and therefore, are not available. However, the results reported by Smyth et al. (1948) are deemed reliable.
One acute inhalation toxicity study has been conducted among the series of acute toxicity tests conducted by Smythet al. (1948). In their investigation, male rats were exposed for a maximum of 8 hours to a flowing stream of air substantially saturated with a vapour of HG, concentrations of which fell into a geometric series with a constant ratio of two. No deaths occurred within the 8-hour exposure time. No other information was available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
Reference:
Composition 0
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 information:
Composition 1
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


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
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1948
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The work of this group pre-dates range finding toxicity guidelines and provided much of the basis for their development. Their results are cited by many subsequent authoritative review bodies and are often found in SIDS and SIAR documents via secondary references. Therefore, these results are deemed reliable.
Reference:
Composition 0
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Strain, sex, and no information of type of inhalation exposure or vehicle, no dose levels were reported, no information on animals or environmental conditions
GLP compliance:
no
Remarks:
study pre-dates GLP requirements
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
-No information reported

ENVIRONMENTAL CONDITIONS
-No information reported

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: no data
Details on inhalation exposure:
Rats are exposed to a flowing stream of air substantially saturated with vapors of the test material, prepared by passing it through a fritted disc bubbler at room temperature for periods of time falling into a geometric series with a constant ratio of two, up to eight hours maximum.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
Concentrations used fall in a series differing by a ratio of 2, and they are approximations because they are estimated from the settings of a proportioning pump and flowmeter rather than being determined analytically.
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
Animals were observed for 14 days after adminstration
Statistics:
No information reported
Sex:
not specified
Dose descriptor:
LC0
Effect level:
other: saturated vapor concentration
Based on:
test mat.
Exp. duration:
8 h
Remarks on result:
other: No mortality was observed
Mortality:
Not reported
Clinical signs:
Not reported
Body weight:
Not reported
Gross pathology:
Not reported
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Conclusions:
Maximum time for no death was reported to be 8 hours, concentration was not reported. LC50 > the saturated vapour concentration at room temperature.
Executive summary:

When groups of 6 rats were exposed for 8 hours to air saturated with hexylene glycol at room temperature (about 60 ml/m3), all animals survived without symptoms (no other details).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987 followed; reliability scoring based on 2002 guideline
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
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: Males were 6 to 8 weeks old and females were 9 to 10 weeks old
- Weight at study initiation: Males 260 - 284 g; Females 229 - 239
- Fasting period before study: None
- Housing: The rats were individually caged in suspended stainless steel mesh cages
- Diet (e.g. ad libitum): SQC(E) Rat and mouse maintenance diet No 1, from Special Diets Services, Ltd, Witham was available ad libitum
- Water (e.g. ad libitum): Mains water was provided ad libitum via cage-mounted water bottles
- Acclimation period: 8 days


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


Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: area of the dorsum cover by a 5 X 5 cm dense gauze patch
- % coverage: 10% of total body surface
- Type of wrap if used: patch was kept in place by a elasticated, open weave adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): swabbed with moist cotton wool

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.22 mL/kg body weight
- Constant volume or concentration used: no, individual dose volumes were calculated from the body weights of the rats on the morning of dosing using the 2.22 mL/kg body weight dose volume and the specific gravity of the test article (0.9 g/mL)

Duration of exposure:
24 hour
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: rats were weighed the day before dosing, on day the day of dosing and days 8 and 15. Clinical signs were recorded frequently on day 1 and regularly for the remainder of the study with the minimum schedule being at least once within half an hour of dosing, four times within 4 hours of dosing, twice daily on days 2, 3, and 4 and once daily from the 5th to last day of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: the conditions of each dermal test site was recorded following removal of dressing on day 2. Full necropsy was performed on day 15 and included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the dermal test site, liver and kidneys
Statistics:
Not reported
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Mortality:
No deaths occured
Clinical signs:
No clinical signs
Body weight:
A small weight loss occured in one female on day 15, and no other significant effects occured.
Gross pathology:
Renal pelvic dilatation in 2 rats and an enlarged spleen on one other animal. There were no irritation reactions or other dermal changes in the sites of application of the test article.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Conclusions:
A single (24 hour) semi-occluded topical application of hexylene glycol to rats at a dose level of 2000 mg/kg body weight caused no death. No clinical signs of systemic toxicity or dermal reactions to application of the test article were apparent during the observation period. The acute median lethal dermal dose (LD50) and acute minimum lethal dose of hexylene glycol were found to exceed 2000 mg/kg body weight.
Executive summary:

An acute dermal toxicity study on hexylene glycol has been performed in accordance with OECD Guidelines for the Testing of Chemicals No. 402 and in compliance with GLP (Gardner, 1996). The study was performed in Crl:CD BR rats in which 5 male and 5 female animals were dermally administered 2000 mg/kg body weight of hexylene glycol in a volume of 2.22 mL/kg body weight. The test substance was applied to the dorsal area (10% of total body surface) under semi-occlusive conditions for an exposure period of 24 hours. Animals were observed over a 15-day period. There were no irritation reactions or other dermal changes at the sites of hexylene glycol application. In addition, no deaths occurred and no clinical signs of systemic toxicity were observed. A small loss in weight loss was observed in one female on day 15, but no other effects on body weight were observed. Gross pathology revealed renal pelvic dilatation in 2 rats and an enlarged spleen in one other animal. The dermal LD50 of hexylene glycol was determined to be greater than 2000 mg/kg body weight in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

Not classification is warranted according to CLP (EC 1272/2008).