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Description of key information

Acute oral toxicity 
The acute toxicity of isopentyl p-methoxycinnamate was evaluated in two studies in male and female Sprague-Dawley rats using the oral and the dermal route of application.
In the oral toxicity study, LD50 values of 9,900 mg/kg bw and 9,600 mg/kg bw, were obtained for males and females, respectively.
Acute dermal toxicity
In the dermal toxicity study, the LD50 value was determined to be greater than 20,000 mg/kg bw.
Thus, isopentyl p-methoxycinnamate showed a very low degree of acute toxicity after administration by either route.
Acute inhalation toxicity
The acute inhalative toxicity of isopentyl p-methoxycinnamate was not studied, since the inhalative route is not considered relevant for this compound. 
This assumption is based on the facts that the vapour pressure of isopentyl p-methoxycinnamate is low (0.000014 hPa at 25°C, see section 4.6 of this IUCLID dataset) and exposure to aerosols, particles, or droplets of an inhalable size is unlikely, since isopentyl p-methoxycinnamate is exclusively used as a sunscreen agent in cosmetic products like solar oil which are not applied as a spray. Moreover, the conditions used in the manufacturing and formulation process of isopentyl p-methoxycinnamate not suggest a significant exposure via air.

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:
May - July 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The study appears scientificially sound and is well documented, but no information on guidelines followed and GLP status are available.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Reference:
Composition 1
Principles of method if other than guideline:
The study was aimed at obtaining knowledge on the signs of poisoning, the lowest toxic dose, and the lethal dose (LD50) of isopentyl p-methoxycinnamate with single peroral administration to rats.
The experimental animals consisted of male and female Sprague-Dawley rats (an outbred strain from the firm S. IVANOVAS GmbH & Co., Med. Experimental Animal Breeds KG (Kißlegg/ Allgäu, Germany). The animals, with weights between 100 and 105 g, were aged 38 (males) and 42 (females) days.
The animals were housed singly in MAKROLON (type II) cages at a room temperature of 24±0.5°C (maximum limit), and a relative humidity of 60±3 % (maximum limit).
The test substance was available in the original liquid form and given undiluted in a signle administration by gavage. The feed (ALTROMIN 1323 from the ALTROMIN GmbH, Lage/Lippe, Germany) was removed 15 - 16 h prior to application, whereas tap water remained available ad libitum.
There was a recovery period of four weeks, during which time the behavior, feed intake, and body-weight development were monitored. At the end of this period, all animals were necropsied and examined macroscopically.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The experimental animals consisted of male and female Sprague-Dawley rats (an outbred strain from the firm S. IVANOVAS GmbH & Co., Med. Experimental Animal Breeds KG (Kißlegg/Allgäu, Germany). The animals, with weights between 100 and 105 g, were aged 38 (males) and 42 (females) days.
The animals were housed singly in MAKROLON (type II) cages at a room temperature of 24±0.5°C (maximal limit), and a relative humidity of 60±3 % (maximal limit).
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was available in the original liquid form and given undiluted in a single administration by gavage. The feed (ALTROMIN 1323 from the ALTROMIN GmbH, Postfach 285, 4937 Lage/ Lippe) was removed 15 - 16 hours prior to application, whereas tap water remained available ad libitum.
Doses:
Dose intervals were based on a factor of 1.26.
Tested doses: 3180, 4000, 5040, 6350, 7900, 9600, 9900 and 10000 mg/kg bw.
No. of animals per sex per dose:
Ten male and ten female animals were used per dose.
Control animals:
not specified
Details on study design:
There was a recovery period of four weeks, during which time the behaviour, feed intake, and body weight development were monitored. At the end of this period, all animals were necropsied and examined macroscopically.
Statistics:
no data
Preliminary study:
none
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 9 900 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 9 600 mg/kg bw
Mortality:
LD50 (7 days) : Sedation, ataxia, (4000 mg/kg p.o.), slow shallow breathing, reduced feed intake (5040 mg/kg p.o.), increased lacrimination, prone position, cataleptonic conditions, general reflexes are difficult to trigger, coma (10000 mg/kg p.o.). Death occured 10-24 h after application in coma.
Clinical signs:
see section "Any other information including tables" below
Body weight:
no data
Gross pathology:
Necropsy: animals found dead showed pale parenchymal organs.
Other findings:
see below

3180 mg/kg p.o.: No indication od toxic reactions. Necropsy: no specific pathological findings

4000 mg/kg p.o.: About 50 min after application, slight sedation and ataxia of all animals for 1 - 3 h. Necropsy: no specific pathological findings

5040 mg/kg p.o.: 30 - 60 min. after application, slight sedation and ataxia of all animals for 2 - 6 h; accompanied by slow and shallow breathing. Necropsy: no specific pathological findings.

6350 mg/kg p.o: About 30 min. after application, medium sedation and ataxia of all animals for 24 - 36 h. Slow, shallow breathing for about 4 - 6 h. Necropsy: no specific pathological findings

7900 mg/kg p.o. : About 30 min. after application, medium sedation and ataxia of all animals for 24 - 48 h. Slow, shallow breathing for about 4 - 6 h. Necropsy: no secific pathological findings.

10000 mg/kg p.o. : 20 - 30 min. after application, all animals revealed severe sedation, ataxia and increased lacrimation; phases of prone position and cataleptonic conditions. Slow and shallow breathing for about 6 h, general reflexes are difficult to trigger. In 6 males and 8 females, sedation deepened to coma 4 - 40 h after application. Death occured in coma, 12 - 24 h after application. Necropsy: pale parenchymal organs in animals found dead. Surviving animals showed no specific pathological findings.

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Isopentyl p-methoxycinnamate was found to posses a low degree of toxicity, with the LD50 value being 9,900 mg/kg bw and 9,600 mg/kg bw, for male and female rats, respectively.
Executive summary:

The acute toxicity of isopentyl p-methoxycinnamate upon oral administration to male and female rats. The test item was found to posses a low degree of toxicity, with the LD50 value being 9,900 mg/kg bw and 9,600 mg/kg bw, for male and female rats, respectively.

At the highest dose level of 10000 mg/kg bw, all animals revealed severe sedation, ataxia and increased lacrimation as well as phases of prone position and cataleptonic conditions at 20 -30 min after application. Slow and shallow breathing was observed for about 6 hours, general reflexes were difficult to trigger. In 6 males and 8 females, sedation deepened to coma 4 - 40 h after application. Death occurred in coma, 12 - 24 h after application. Necropsy revealed pale parenchymal organs in animals found dead. Surviving animals showed no specific pathological findings.

Endpoint conclusion
Dose descriptor:
LD50
9 600 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
February to June 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The animals belonged to the Sprague Dawley (Him:OFA) strain and were SPF
Supplier: Forschungsinstitut für Versuchstierzucht, A-2325 Himberg, Austria
Number: 20 males and 20 females
Age at the beginning of the study: 8 to 12 weeks.
Hygiene: improved open hygienic conditions.
Room temperature : average of 23 °C
Relative humidity: average of 55 %
Light: artificial light from 7 a.m. to 7 p.m.
Cages: single caging in Makrolon cages type II
Food: Altromin 1314 ff, 10kGy gamma-irradiated, ad libitum
Water : tap water, acidified with HCl to pH 5, ad libitum
Acclimatisation period: 5 d
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test substance was applied once to the dorsal skin of the rats.
Duration of exposure:
The duration of the exposure was 24 h.
Doses:
The test substance was applied once to the dorsal skin of the rats in doses of 2500, 5000, 10000, and 20000 mg per kg body weight (bw).
No. of animals per sex per dose:
Isopentyl p-methoxycinnamatewas administered to 4 groups of 5 male and 5 female rats each.
Control animals:
not specified
Details on study design:
Sacrifice: 14 d after administration of the test substance.
Statistics:
A one-way analysis of variance (p=0.05) was used to evaluate differences in body weights.
Preliminary study:
No preliminary study was conducted.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Mortality:
No animal died spontaneously during the experiment.
Clinical signs:
Animal No. 32 lost the linen dressing and the patch 8 h after the administration. In all animals, chromodakryorrhoea was found within the first 24 h after administration. This unspecific change was caused by the reduced wellbeing by the dressing and is not assumed to be a test substance-related effect.
Body weight:
There was no statistically significant difference of body weight between the groups. The body weight gain was slightly lesser n the first week than in comparable untreated rats. Body weight gain was inconspicuous in the second week p.a. This slight reduction in body weight gain, mainly in the females, is regarded to be a test substance related effect.
Gross pathology:
Pathological changes were detected only in 2 animals. Both animals showed hydrometra, a known spontaneous change of this strain of rats, caused by a pronounced intensity of oestrus cycle. These changes are not assumed to have been caused by the test substance.
Other findings:
not applicable

not applicable

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
The test substance caused no alterations or toxic signs in the animals, except a slightly reduction of body weight gain in the first week.
The LD50 (dermal, 14d) was determined to be greater than 20,000 mg/kg bw. Thus, isopentyl p-methoxycinnamate was shown to possess a low degree of toxicity when administered at single dermal doses to male and female rats.
Executive summary:

The acute toxicity of isopentyl p-methoxycinnamate after dermal application to rats was studied.

Isopentyl p-methoxycinnamate was administered to 4 groups of 5 male and 5 female Sprague-Dawley rats each. The test substance was applied once to the dorsal skin of the rats in doses of 2,500, 5,000, 10,000, and 20,000 mg/kg bw.

Methods and investigations performed were in conformance with OECD guideline no. 402, "Acute Dermal Toxicity".

The test substance did not cause any alterations or toxic signs in the animals, except of a slight reduction of body weight gain in the first week. No test substance-related morphological lesions were observed at necropsy.

The LD50(dermal, 14 d) was determined to be greater than 20,000 mg/kg bw. Thus, isopentyl p-methoxycinnamate was shown to possess a low degree of toxicity when administered at single dermal doses to male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
20 000 mg/kg bw

Additional information

Acute oral toxicity

In the acute oral toxicity study of isopentyl p-methoxycinnamate in rats, the test item was administered undiluted by gavage to male and female Sprague-Dawley rats (10 animals per dose) at dose levels of 3,180, 4,000, 5,040, 6,350, 7,900, 9,600, 9,900, and 10,000 mg/kg bw. Isopentyl p-methoxycinnamate was found to possess a low degree of toxicity, with the LD50 value being 9,900 mg/kg bw and 9,600 mg/kg bw, for male and female rats, respectively.

At the highest dose level, all animals revealed severe sedation, ataxia and increased lacrimation as well as phases of prone position and cataleptonic conditions at 20-30 min after application. Slow and shallow breathing was observed for about 6 h, general reflexes were difficult to trigger. In 6 males and 8 females, sedation deepened to coma 4-40 h after application. Death occurred in coma, 12-24 h after application. Necropsy revealed pale parenchymal organs in animals found dead. Surviving animals showed no specific pathological findings.

Acute dermal toxicity

In the acute dermal toxicity study, isopentyl p-methoxycinnamate was occlusively applied to the dorsal skin of Sprague-Dawley rats (4 groups of each 5 males and 5 females) in doses of 2,500, 5,000, 10,000, and 20,000 mg/kg bw. The study was performed according to OECD guideline no. 402.

The test substance did not cause any alterations or toxic signs in the animals, except of a slight reduction of body weight gain in the first week. No test substance-related morphological lesions were observed at necropsy. The LD50 was determined to be greater than 20,000 mg/kg bw.

 


Justification for selection of acute toxicity – oral endpoint
Guideline study

Justification for selection of acute toxicity – dermal endpoint
Guideline study

Justification for classification or non-classification

Based on the results of the two studies mentioned above, it can be concluded that isopentyl p-methoxycinnamate has a very low toxicity to rats after a single oral or dermal administration. According to the current EU-CLP criteria, this compound cannot be classified with respect to its acute oral or dermal toxicity, as the LD50 values for both endpoints exceed the range given for all four categories of the EU-CLP system. No risk phrase is required.

A classification of isopentyl p-methoxycinnamate with respect to its acute inhalation toxicity is not possible, as no data for this endpoint are available.