Hexahydro-4,7-methano-1H-indenyl acrylate

Endpoint summary

Description of key information

Dicyclopentadienyl acrylate is virtually nontoxic after a single ingestion and of low toxicity after short-term skin contact. The inhalation of a highly saturated vapour-air-mixture represents an unlikely acute hazard.
Oral: LD50 = ca. 10000 mg/kg bw (Sprague-Dawley rat, BASF Test comparable to OECD TG 401)
Dermal: LD50: ca. 4881 mg/kg bw (New Zealand White rabbit, occlusive)
Inhalation: LC0 = approx. >= 1.0 mg/L (nominal, saturated vapour, 7 h) (Sprague-Dawley rat, IHT comparable to OECD 403, adopted 1981)

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:

other: Comparable to guideline study, well documented and acceptable for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(adopted 1981)

Deviations:

yes

Remarks:

Only two doses tested (as compared to three or more as recommended in the guideline)

Principles of method if other than guideline:

according to BASF-internal standard

GLP compliance:

no

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:

- Mean body weight of male animals: 205 g; mean body weight of female animals: 180 g
- Diet (ad libitum): HERITAN MRH-Haltung, complete diet for mice, rats, and hamsters, Heinrich Eggersmann, Rinteln.
- Water (ad libitum): tap water

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

0.5% CMC solution (concentration 50% w/v)

Doses:

6810 and 10000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No statistics performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 10 000 mg/kg bw

Based on:

test mat.

Mortality:

6810 mg/kg bw: 1/5 females after 14 days
10000 mg/kg bw: 1/5 females and 3/5 males after 14 days

Clinical signs:

other: In the 1st test week: Loss of weight, protracted onset of death and poor general state. Nonspecific signs as apathy, aggressiveness, staggering, tremor, spastic gait, diarrhoea.

Gross pathology:

Animals that died: Heart: acute dilatation and acute passive hyperemia; stomach: dilatation; intestines: atonic.
Sacrificed animals: Organs: no abnormalities detected

Mortality:

 

Dose [mg/kg bw]	Conc. [%]	No. of animals/sex	Dead animals / treated animals after
			1 h	24 h	48 h	7 d	14 d
10000	50.0	5 m	0/5	0/5	0/5	3/5	3/5
		5 f	0/5	0/5	0/5	1/5	1/5
6810	50.0	5 m	0/5	0/5	0/5	0/5	0/5
		5 f	0/5	0/5	0/5	1/5	1/5

m: male

f: female

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

10 000 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:

other: Basic data given: study report which meets basic scientific principles, acceptable with restrictions (limited documentation)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(adopted 1981)

Deviations:

yes

Remarks:

no analytical verification of the test atmosphere concentrations

Principles of method if other than guideline:

The inhalation hazard test was conducted according to the method described by Smyth et al. (1962).
Smyth HF et al. (1962). Am. Ind. Hyg. Ass. J. 23: 95-107.

GLP compliance:

no

Test type:

other: Inhalation Hazard Test

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Mean body weight of animals:
- males: 253 g (test group 1); 259 g (test group 2);
- females: 188 g (test group 1); 180 g (test group 2).

- Diet (ad libitum): HERITAN MRH-Haltung, complete diet for mice, rats, and hamsters, Heinrich Eggersmann, Rinteln.
- Water (ad libitum): tap water

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Inhalation of an atmosphere enriched with vapour at 20°C. For enrichment, 200 L air/h was conducted through a Iayer of about 5 cm of the product.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

7 h

Concentrations:

Mean concentration: approx. 1 mg/L

No. of animals per sex per dose:

6 animals/sex/dose (two groups)

Control animals:

yes

Statistics:

none

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 1 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

7 h

Remarks on result:

other: IHT: No mortality was observed when 12 rats were exposed for 7 hours to an atmosphere that had been saturated at 20°C with the volatile parts of the compound.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed.

Body weight:

Body weight
- males: 317 g (test group 1), 333 g (test group 2);
- females: 290 g (test group 1), 201 g (test group 2)

Gross pathology:

Nothing abnormal detected.

The test substance concentration was estimated to be approx. 1 mg/L at 20 °C. Vapour saturation was calculated to be approx. 0.11 mg/L at 20 °C. Concentrations above the vapour saturation treshold should carefully be considered to be aerosols. Thus, the animals were exposed to a saturated vapour atmosphere, possibly in the presence of some aerosol particles.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

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:

other: Secondary literature, comparable to guideline study without detailed information. Documentation peer-reviewed.

Principles of method if other than guideline:

Method is described in Smyth (1962).

GLP compliance:

no

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 - 3.5 kg

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

no data

No. of animals per sex per dose:

4

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Statistics:

LD50 was calculated according to Thompson (1947).

Sex:

male

Dose descriptor:

LD50

Effect level:

4 881 mg/kg bw

Mortality:

A LD50 was calculated to be 4.52 (2.08 - 9.8) ml/kg bw , corresponding to 4881 (2246 - 10584) mg/kg bw.

Interpretation of results:

not classified

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 881 mg/kg bw

Additional information

Oral exposure route:

 

In the key study conducted by BASF AG (1980) two groups of 5 Sprague-Dawley rats/sex/dose were administered doses of 6810 and 10000 mg/kg bw dicyclopentadienyl acrylate, respectively (following the principle of OECD TG No. 401, adopted 1981). They were observed for 14 days for lethality and clinical signs of intoxication. In the lower dose group (6810 mg/kg bw) 1/5 females died between 48 h and 7 days. In the higher dose group (10000 mg/kg bw) 1/5 females and 3/5 males died between 48 h and 7 days. The LD50 was found to be ca. 10000 mg/kg bw. The following clinical signs were observed in the first week: loss of weight, protracted onset of death and poor general state. Nonspecific signs as apathy, aggressiveness, staggering, tremor, spastic gait, and diarrhoea were observed. The necropsy revealed acute dilatation and acute passive hyperemia (heart), dilatation in the stomach, and atony in the intestines in the animals that died. No abnormalities were observed in the animals sacrificed.

 

In a supporting study (BASF AG, 1966) 5 rats/sex/dose were administered doses of 216, 1728, 3456, 6912 mg/kg bw dicyclopentadienyl acrylate. No mortality was observed, thus the LD50 was greater than 6912 mg/kg bw. The following clinical signs were found: apathy, atony, staggering, piloerection, exophthalmus.

 

In a third study (BASF AG, 1964) 5 rats/sex/dose (lowest dose 5 male, 4 female) were administered doses of 216, 1728, 3456, 4320, 5400, and 6912 mg/kg bw. No mortality was observed until 3456 mg/kg bw. In the higher doses mortality rates of 2/10 (4320 mg/kg bw), 4/10 (5400 mg/kg bw), and 9/10 (6912 mg/kg bw) were observed. Most of the animals died within 48 h and 7 d after treatment. An LD50 of 5400 mg/kg bw was deduced from these results. The following clinical signs were found: Apathy, dyspnea, late deaths, eye discharge, laboured breathing, piloerection. No abnormal findings were observed after necropsy.

 

Based on these test results dicyclopentadienyl acrylate was virtually nontoxic after a single ingestion.

No classification and labelling according to Annex VI of Directive 67/548/EEC and according to REGULATION (EC) No 1272/2008 is proposed.

 

Dermal exposure route:

 

Results from one reliable publication are available for dermal exposure route (Carpenter et al., 1974). 4 male New Zealand White rabbits per dose were exposed to dicyclopentadienyl acrylate (occlusive, unchanged) for 24 h. An LD50 was calculated to be 4881 (2246 - 10584) mg/kg bw. Based on these test results dicyclopentadienyl acrylate was of low toxicity after short-term skin contact. No classification and labelling according to Annex VI of Directive 67/548/EEC and according to REGULATION (EC) No 1272/2008 is proposed.

Inhalation exposure route:

 

In the key study (BASF AG, 1980) an inhalation hazard test was performed in Sprague-Dawley rats. Six male and six female rats were exposed (whole-body) to dicyclopentadienyl acrylate (20°C) at a nominal concentration of 1 mg/L (no analytical monitoring of the test atmosphere concentration) for 7 hours. No mortality and no clinical signs/necropsy findings were observed, thus deducing an LC0 of >= 1 mg/L air.

 

Another inhalation hazard test (BASF AG, 1966) was performed with a nominal concentration of 0.44 mg/L air for 8 h. No mortality was observed. The following clinical signs were observed: slight mucosal irritation, escape attempts. An LC0 of >= 0.44 mg/L air was deduced.

 

Another inhalation hazard test (BASF AG, 1964) was performed with a nominal dic concentration of 0.069 at 20 °C and 1.64 mg/L air at 50 °C for 8 h, respectively. No mortality was observed. In the higher dose group attempts to escape were observed at the start of the experiment, additional to slight eye and nasal secretion. No necropsy findings were noted. An LC0 of >=1.64 mg/L air was deduced.

 

Based on these test results dicyclopentadienyl acrylate was virtually nontoxic after inhalation for 8 h up to a concentration of 1.64 mg/l (nominal),

Thus, the inhalation of a highly saturated vapour-air-mixture represents an unlikely acute hazard.

Justification for selection of acute toxicity – oral endpoint
The key study was selected

Justification for selection of acute toxicity – inhalation endpoint
The key study was selected

Justification for selection of acute toxicity – dermal endpoint
The key study was selected

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

-no classification required for acute toxicity

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008 (last amended by EC/286/2008 (2011-03-10)):

- Oral route: no classification required

- Dermal route: no classification required

- Inhalation route (vapour): no classification required