Registration Dossier

Administrative data

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.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no details given

Test animals

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).

Administration / exposure

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

Results and discussion

Preliminary study:
none
Effect levelsopen allclose all
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

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.