Hexamethylene diacrylate

Endpoint summary

Description of key information

Oral: LD50 (rat) > 5000 mg/kg bw (comp. OECD 401) (BASF, 1979)
Inhalation: Rat, IHT: 7 h: LC50 > 0.41 mg/l air (BASF, 1979)
Dermal: Rabbit: LD50 = 3650 mg/kg bw (Litton Bionetics, 1972)

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

In principle, the methods described in the OECD Guideline 401 were used. Young adult laboratory rats were purchased from breeder. Several groups of 5 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in suitable vehicle. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 14 day study period.

GLP compliance:

no

Remarks:

; GLP was not compulsory at the time the study was conducted

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation:
mean body weight, males: 160 g in the 5000 mg/kg b.w. group
mean body weight, males: 140 g in the 2150 mg/kg b.w. group
mean body weight, females: 150 g in the 5000 mg/kg b.w. group
mean body weight, females: 160 g in the 2150 mg/kg b.w. group
- Fasting period before study:
15-20 hours
- Diet: Herilan MRH-Haltung; H. Eggersmann KG (ad libitum)
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 % and 21.5 % for the 5000 and 2150 mg/kg b.w. dose level, respectively
- Amount of vehicle (if gavage): 10 ml/kg b.w.

Doses:

2150, 5000 mg/kg b.w.

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

Duration of observation period following administration:
14 days
- Frequency of observations and weighing:
Animals were observed and examined for clinical signs of toxicity during the first hour following application, after 4 and 5 hours and further on day 1, 2, 3, 6, 8, 9, 10 and 13 after dosing.
Mean body weights were determined for the following intervals of time: 2-4, 6-7 and 9-13 days of the study.
- Necropsy of survivors performed: yes
Deceased animals and those sacrificed at the end of the observation period were necropsied.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: One female in the 5000 mg/kg bw dose group died during the observation period, at day 7 after application

Mortality:

All males survived. One female in the 5000 mg/kg bw dose group died during the observation period, at day 7 after application.

Clinical signs:

other: No signs of toxicity were reported for the low dose group. For the high-dose group dyspnea (2 cases), aggressiveness (1 case), spastic walk (1 case) and bad general condition (1 case) were reported only at day 3 after application.

Gross pathology:

Necropsy of the female rat that died at day 5:
Acute congestion of the heart and dilatation of the atrium, substance-coloured content in gastrointestinal tract.

Necropsy of the survivors which were sacrificed after the end of the observation period of 14 days:
Findings were observed in the stomach and included thickening and plication of forestomach as well as its agglutination with liver, peritoneum, and spleen.

Table 1: Mean body weight of rats after oral application of Hexandiolacrylate, technical grade

	Males		Females
Dose level [mg/kg bw]	5000	2150	5000	2150
Day 2-4	170	171	146	182
Day 6-7	196	200	169	193
Day 9-13	239	212	192	193

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

BASF-Test
The inhalation hazard test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at the temperature chosen for vapor generation (usually 20°C). Several groups of usually 3 rats per sex were sequentially exposed to the vapors, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted disc in a glass cylinder for different time periods.
No analytical determination of the atmosphere concentrations was performed. The nominal concentration usually can be calculated as quotient of the amount of the test substance weight loss during exposure. Group-wise documentation of clinical signs was performed over the 14 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period in surviving animals.

GLP compliance:

no

Remarks:

; GLP was not compulsory at the time the study was conducted

Test type:

other: Inhalation hazard test

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation:
mean body weight, males: 184.2 g in the treated group
mean body weight, males: 200 g in the control group
mean body weight, females: 200 g in the treated group
mean body weight, females: 194 g in the control group
- Diet: Herilan MRH-Haltung; H. Eggersmann KG (ad libitum)
- Water: ad libitum

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: The animals were exposed to atmosphere saturated with the volatile parts of the test material in the air at 20 °C.

Details on inhalation exposure:

Saturation of the atmosphere was generated by conducting an air stream through a substance layer of 5 cm height.
The rats were exposed to the test atmosphere for 7 hours.
Air flow was 200 l/h in the exposure chamber.
The control animals were shame-exposed.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

7 h

Concentrations:

The concentration was 0.41 mg/l (20 °C), the nominal concentration was calculated as quotient of the amount of the test substance weight loss during exposure.

No. of animals per sex per dose:

3 animals per sex per group

Control animals:

no

Details on study design:

The exposure time not causing lethality was tested twice.
- Duration of post exposure period until necropsy: 14 days
- Frequency of weighing: Test animals were weighed at test initiation only
- Frequency of observations: The animals were observed following exposure after 3 min, 10 min, 30 min, 1 hour, 3 hours, 7 hours and thereafter daily for the first 3 days after test initiation
- Necropsy of survivors performed: yes. The necropsy of the animals was done on day 14 following exposure

Sex:

male/female

Dose descriptor:

LC0

Effect level:

0.41 mg/L air

Exp. duration:

7 h

Remarks on result:

other: All 12 animals exposed to the test material survived.

Mortality:

All animals exposed to the test material survived, as well as all controls.

Clinical signs:

other: In both treated groups, accelerated intermittent breathing, snout-wiping and unkempt fur were reported during and after exposure; at day 3 of observation, no more symptoms were seen. Therefore the animals were no more observed until day 14, i.e. the day o

Body weight:

Only initial body weights were recorded.

Gross pathology:

Necropsy of the animals sacrificed on day 14 was inconspicuous.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

0 mg/m³ air

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

: occlusive conditions for 24 h; no data on body weight, clinical signs and gross pathology.

GLP compliance:

no

Remarks:

; GLP was not compulsory at the time the study was conducted.

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

other: albino

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

The animals were prepared by careful removal of the hair with electric clippers. Planned areas of application were identified. After weighing the animal the calculated dose was applied and the entire area covered with rubber dam and held in place by tape.

Duration of exposure:

24 h

Doses:

0.315, 0.795, 1.99 and 5.0 ml/kg bw

No. of animals per sex per dose:

4 animals per dose (only 3 at 1.99 mg/kg bw)

Control animals:

other: the untreated sites of the same animal served as control

Details on study design:

24 h after exposure, the binders were removed and an effort made to remove any remaining material from the skin surface.
A score of the local effects, according to the method of Draize, was recorded. The animals were observed repeatedly for seven days at the end of which time they were sacrificed. Necropsy was performed and samples of any abnormal tissues were preserved in 10 % formalin for possible future histopathologic examination.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 650 mg/kg bw

Remarks on result:

other: original value given as 3.6 ml/kg bw

Mortality:

No deaths occured at doses of 0.315 and 0.795 mL/kg bw. At 1.99 mL/kg bw one animal out of three died and at 5.0 mL/kg bw two out of four animals died.

Clinical signs:

other: no data given

Gross pathology:

no data given

Other findings:

The test material produced only slight to moderate erythema and edema and was not scheduled for the primary skin irritation test

Conclusions:

The LD50 for acute dermal toxicity in rabbit was 3650 mg/kg bw 1,6-Hexanediol Diacrylate (original value was given as 3.6 ml/kg bw) under the experimental test conditions chosen.
Therefore, the test material fulfils the requirements to be classified as Category 5 according to GHS-UN criteria. According to EU criteria (1272/2008/EC), a non-classification is warranted.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 650 mg/kg bw

Additional information

There are valid data available for the assessment of the acute toxicity of 1,6-hexanedioldiacrylate. 

Oral

In a standard acute test, comparable to OECD guideline 401, five male and five female Sprague-Dawley rats were treated with 2150 and 5000 mg/kg bw 1,6-hexanedioldiacrylate under standardized conditions. The animals were observed for 14 d, the LD50 was >5000 mg/kg bw for male and female rats. All males survived. One female in the 5000 mg/kg bw dose group died during the observation period, at day 7 after application. No signs of toxicity were reported for the low dose group. For the high-dose group, dyspnea (2 cases), aggressiveness (1 case), spastic walk (1 case) and bad general condition (1 case) were reported only at day 3 after application. Necropsy of the female rat that died at day 7 revealed acute congestion of the heart and dilatation of the atrium, as well as substance-coloured content in gastrointestinal tract. Necropsy of the survivors which were sacrificed after the end of the observation period of 14 days revealed findings in the stomach and included thickening and plication of forestomach as well as its agglutination with liver, peritoneum, and spleen (BASF, 1979).

In another acute oral toxicity study, 5 Sprague Dawley rats per dose were treated with 50, 127.5, 315.1, 795, 1999 and 5000 mg/kg bw of the test material by gavage. Animals were observed frequently during the first 4 hours, and at least daily thereafter for 14 days. No mortalitiy occured at doses up to 1999 mg/kg bw. In the highest dose group 2/5 animals died. Both deaths occured during the first night. No signs of toxicity were observed. The LD50 was >5000 mg/kg bw (Litton Bionetics, 1972).

 

Inhalation

In a standardized inhalation hazard test with a saturated vapour atmosphere, 0/12 rats died after 7 h exposure. The LC0 is 0.41 mg/l air for male and female rats. Accelerated intermittent breathing, snout-wiping and unkempt fur were reported during and after exposure; at day 3 of observation, no more symptoms were seen. Therefore the animals were no more observed until day 14, i.e. the day of necropsy. Necropsy was inconspicuous (BASF, 1979).

Dermal

In an acute dermal toxicity study, 4 albino rabbits per dose were treated with 0.315, 0.795, 1.99 and 5.0 ml/kg bw of the test material for 24 hours under occlusive conditions. The animals were observed repeatedly for seven days at the end of which time they were sacrificed. No deaths occured at doses of 0.315 and 0.795 ml/kg bw. At 1.99 ml/kg bw one animal out of three died and at 5.0 ml/kg bw two out of four animals died. The LD50 was 3650 mg/kg bw 1,6-Hexanediol Diacrylate (original value was given as 3.6 ml/kg bw) (Litton Bionetics, 1972).

Justification for classification or non-classification

The oral LD50 is > 5000 mg/kg bw for male and female rats. Since in an inhalation hazard test with rats exposed to a saturated vapour atmosphere of the test material for 7 h revealed no mortality and only transient clinical signs.  1,6-hexanedioldiacrylate cause slight acute toxicity via the dermal route, as the LD50 in a reliable study was 3650 mg/kg bw. The available data for 1,6-hexanedioldiacrylate indicate a relative low potential for acute toxicity.

Based on the results, the test item is no subject to classification and labelling according to Regulation (EC) No 1272/2008 (CLP). The test material fulfils the requirements to be classified as acute dermal cat. 5 according to GHS-UN criteria.