p-cymene

Endpoint summary

Description of key information

Acute oral toxicity:

In the key acute oral study of Jenner et al. (1964), groups of 10 male and 10 female Osborne-Mendel rats were orally administered undulitued p-Cymene at various doses (not specified) to calculate an oral LD50. Rats were monitored for up to 2 weeks. The death time for p-Cymen was indicated between 4 hr-2 weeks.

Rats showed depression shortly following dosing. The coma, bloody lacrimation, diarrhea with irritable, scrawny appearance during were noted the observation period. The LD50 was calculated using the method of Litchfield & Wilcoxon (1949). LD50 was determined to be 4750 mg/kg bw (95% confidence limits: 3720-6060) with a slope function of 1.7.

Acute dermal toxicity:

In a study report of Moreno (1973), ten rabbits were dermally treated with p-Cymene at 5000 mg/kg bw. The animals were observed for any signs of toxicity and death for 14 days. All rabbits survived the treatment. No signs of toxicty were reported. Skin irritation was graded as follows: slight redness (3/10), moderate redness (7/10), slight edema (3/10), and moderate edema (7/10). Based on the results, the LD50 was estimated to be greater than 5000 mg/kg bw.

Acute inhalation toxicity:

In the unpublished reports of MacDonald (1962), rats and guinea pigs were exposed to atmospheres saturated with 9.7 mg /L ofp-Cymene for a period of 5 hours. Clinical signs and mortality were recorded. Surviving animals were removed from the exposure chamber and observed for an additional week.

Signs reported during the first 30 minutes were similar for both species and were typical for irritation: excitement, pawing at the eyes and nose, increased blinking, squinting, and eye closure.

In rats, after 45 minutes, equilibrium loss and increased salivation were noted. One-half hour later, fine tremors began and increased to quivering after another 15 minutes. Clonic convulsions were reported after another 15 minutes and the rats staggered about aimlessly until the end of the exposure.

In guinea pigs, approximately 90 minutes following exposure, 1 guinea pig had a 10-15-second violent clonic convulsion followed by prolonged quivering. Afterwards, this guinea pig continued to exhibit clonic convulsions of varying degrees. The second guinea pig began quivering at about 120 minutes into the exposure and had a clonic convulsion about 30 minutes later. By the end of the exposure period, both guinea pigs were comatose and had continuous clonic convulsions.

The morning after the exposure, the rats and guinea pigs appeared fully recovered.  

 

A "lethal concentration time value (LCt)" of >9.7 mg/Lwas calculated based on the "shortest period of exposure causing death", where the concentration was expressed as mg/l and time as minutes.

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:

1964

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

equivalent or similar to guideline

Guideline:

other: method of Litchfield & Wilcoxon (1949)

Principles of method if other than guideline:

- Principle of test: Groups of 10 young adult Osborne-Mendel rats evenly divided by sex were fasted for
approximately 18 hr prior to treatment. Animals had access to water at all times, and food was replaced in cages as soon as animals received their respective doses.
- Short description of test conditions: Undiluted p-Cymene in diffrent concetrations was administrated to all rats by intubation.
- Parameters analysed / observed: ll animals were maintained under close observation for recording toxic signs artd time of death. Such observation was continued until animals appeared normal and showed weight gain. The usual observatiort period was 2 weeks.

GLP compliance:

no

Test type:

other: Acute oral toxicity

Limit test:

yes

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rats:
Osborne-Mendel
- Females and males
- Diet ad libitum
- Water ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Undluted p-Cymene was administrated to male and female rats by oral incubation.

Doses:

Undluted p-Cymene was administrated to rats

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: not specified
- All animals were maintained under close observation for recording toxic signs artd time of death. Such observation was continued until animals appeared normal and showed weight gain.

Statistics:

LD50 was computed by the method of Litchfield & Wilcoxon (1949).

Preliminary study:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 4 750 mg/kg bw

Based on:

test mat.

95% CL:

ca. 3 720 - ca. 6 060

Mortality:

Indicated time of death: 4hr - 2 weeks

Clinical signs:

other: Rats showed depression shortly following dosing and also coma, bloody lacrimation, diarrhea with irritable, scrawny appearance during the observation period

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified because LD50 is greater than the requirements for a Category 4 toxicant (2000 mg/kg) Criteria used for interpretation of results: EU CLP

Conclusions:

Based on the results, The LD50 was calculated to be 4750 mg/kg bw (95% confidence limits: 3720-6060).

Executive summary:

In the study of Jenner et al. (1964), groups of 10 male and 10 female Osborne-Mendel rats were orally administered undulitued p-cymene at various doses (not specified) to calculate an oral LD50. Rats were monitored for up to 2 weeks. The death time after exposure to p-cymene was indicated, as follows: from 4 hr till 2 weeks.

Rats showed depression shortly following dosing. Other clinical signs included: coma, bloody lacrimation, diarrhea with irritable, scrawny appearance during the observation period.

The LD50 was calculated using the method of Litchfield & Wilcoxon (1949). The LD50 was determined to be 4750 mg/kg bw (95% confidence limits: 3720-6060). with a slope function of 1.7

Based on the results, it is concluded that p-Cymene should not be classified as acute oral toxic under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

4 750 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:

accepted calculation method

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Rats were exposed to atmospheres saturated with 9.7 mg /L of pcymene for a period of 5 hours. A "lethal concentration time value (LCt)" was calculated based on the "shortest period of exposure causing death", where the concentration was expressed as mg/l and time as minutes.
- Parameters analysed / observed: Clinical signs and mortality were recorded.

GLP compliance:

no

Test type:

other: Acute inhalation toxicity in rats

Limit test:

yes

Species:

rat

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specifed

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

not specifed

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

ca. 5 h

Concentrations:

Rats were exposed to atmospheres saturated with 9.7 mg /L of p-cymene for a period of 5 hours.

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 30 min, 45 min and 1 day
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Statistics:

A "lethal concentration time value (LCt)" was calculated based on the "shortest period of exposure causing death", where the concentration was expressed as mg/l and time as minutes

Preliminary study:

not applicable

Key result

Sex:

not specified

Dose descriptor:

other: lethal concentration time value (LCt)

Effect level:

> 9.7 mg/L air

Based on:

test mat.

Exp. duration:

5 h

Remarks on result:

other: no deaths

Mortality:

No deaths were reported

Clinical signs:

other: other:

Body weight:

not specified

Gross pathology:

not specified

Interpretation of results:

study cannot be used for classification

Conclusions:

A "lethal concentration time value (LCt)" of >9.7 mg/L was calculated based on the "shortest period of exposure causing death", where the concentration was expressed as mg/l and time as minutes. No deaths were observed during the exposure period. The morning after exposure, the rats appeared fully recovered from the clinical signes observed during the exposure period.
 

Executive summary:

In this study, rats were exposed to atmospheres saturated with 9.7 mg /L of p-Cymene for a period of 5 hours. Clinical signs and mortality were recorded. Surviving animals were removed from the exposure chamber and observed for an additional week.

Signs reported during the first 30 minutes were those typical of irritation: excitement, pawing at the eyes and nose, increased blinking, squinting, and eye closure. After 45 minutes, equilibrium loss and increased salivation were noted. One-half hour later, fine tremors began and increased to quivering after another 15 minutes. Clonic convulsions were reported after another 15 minutes and the rats staggered about aimlessly until the end of the exposure. The morning after exposure, the rats appeared fully recovered.

A "lethal concentration time value (LCt)" of >9.7 mg/Lwas calculated based on the "shortest period of exposure causing death", where the concentration was expressed as mg/l and time as minutes.

 

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

0.01 mg/m³ air

Quality of whole database:

A "lethal concentration time value (LCt)" of >9.7 mg/Lwas calculated

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)

Qualifier:

equivalent or similar to guideline

Guideline:

other: One of a series of range-finding studies using 5 g/kg/bw

Principles of method if other than guideline:

- Principle of test:
Acute dermal toxicty in rabbits

- Short description of test conditions:
Ten rabbits are dermally treated with test material at high dose of 5 g/kg/bw. T

- Parameters analysed / observed:
he animals are observed for any signs of toxicity and death for 14 days.
Skin irritation is monitored.

GLP compliance:

no

Test type:

other: Acute dermal toxicity in rabbits

Limit test:

yes

Species:

rabbit

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rabbits

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

not specified

Duration of exposure:

14 days observation period

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10 animals per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: every day
- Necropsy of survivors performed: not specified
- Other examinations performed: clinical signs, skin irritation

Preliminary study:

no applicable

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were reported

Clinical signs:

other: No toxicity signs were reported. Skin irritation was observed in following animals: slight redness - 3/10 moderate redness - 7/10 slight edema - 3/10 moderate edema - 7/10

Gross pathology:

not specified

Interpretation of results:

other: Not classified because LD50 is greater than the requirements for a Category 4 toxicant (2000 mg/kg) Criteria used for interpretation of results: EU

Conclusions:

Based on the results, the dermal LD50 for p-Cymene was estimated to be greater than 5000 mg/kg bw.

Executive summary:

In this study of Moreno (1973) ten rabbits were dermally treated with p-Cymene at 5000 mg/kg bw.

The animals were observed for any signs of toxicity and death for 14 days. All rabbits survived the treatment. No signs of toxicty were reported.

Skin irritation was graded as follows: slight redness (3/10), moderate redness (7/10), slight edema (3/10), and moderate edema (7/10).

Based on the results, the LD50 was estimated to be greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Justification for classification or non-classification

Based on the results obtained, p-Cymene is not classified for acute oral toxicity and acute dermal toxicty according to the EU CLP regulation, because the calculated oral LD50 of 4750 mg/kg bw (95% confidence limits: 3720-6060) and dermal LD50 > 5000 mg/kg bw are greater than the requirements for a Category 4 toxicant (2000 mg/kg).