α,α'-propylenedinitrilodi-o-cresol

Endpoint summary

Description of key information

LD50 (oral) ca. 1350 mg/kg bw (BASF AG, 1967)
LD50 (dermal) > 2000 mg/kg bw (BASF SE, 2012)

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:

1967

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

only 7 days of observation

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: US-rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: males: 140-234 g, females 115-194 g

ENVIRONMENTAL CONDITIONS
no data

Route of administration:

oral: gavage

Vehicle:

other: aqueous traganth emulsion

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2, 10, 20 or 30 % (V/V)

Doses:

0.2, 1.0, 1.25, 1.6, 2.5, 3.2, 6.4 ml/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology

Statistics:

not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 350 mg/kg bw

Based on:

test mat.

Remarks on result:

other: => ca. 1.5 ml/kg in the study report with a purity of ca. 80 %, density used for calculation: 1.13 g/cm3 for 1.2 ml

Mortality:

0.2 ml/kg => no deaths
1.0 ml/kg => 1/10 animals died
1.25 ml/kg => no deaths
1.6 ml/kg => 6/10 animals died
2.5 ml/kg => 8/10 animals died
3.2 ml/kg => all animals died
6.4 ml/kg => all animals died

Clinical signs:

other: Hunched position, dyspnea, aqueous secretion out of the mouth, blood encrusted eyes and noses, horrent fur, spastic gait. All animals were free of symptoms after 4 days (low dose animals recovered quicker)

Gross pathology:

Animals that died: blood encrusted eyes, smeared anuses, intestines with test substance smell, inflated stomach, diarrhea. Sacrificed animals at end of study: organs without findings

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the available acute oral studies, the substance is classified Acute toxicity oral Cat 4 (according to CLP).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 350 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH
- Age at study initiation: approx. 8 weeks (males); approx. 12 weeks (females)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight); mean weight males: 235.6 g; mean weight females: 208 g
- Fasting period before study: N/A
- Housing: Single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 – 70%
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

olive oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: at least 10% of the body surface
- Type of wrap if used: semiocclusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: after 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg bw
- Concentration (if solution): 50 g/100 mL
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of
observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. A check for any dead or moribund animals was made at least once each workday
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination. Very slight erythema (grade 1) was noted in three male animals at day 1 and persisted in two of these animals until study day 3 or increased to well-defined erythema (grade 2) in the t

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the acute dermal median lethal dose (LD50) of > 2000 mg/kg bw, the substance does not meet the GHS criteria for classification for Acute Demal toxicity

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity: oral

There is no study available, which is performed according to the current guideline. The study with rats (only 7 days post observation) is considered of sufficient and good quality to allow the evaluation of this endpoint and is comparable to OECD 401 guideline. The LD50 in rats (5 animals/sex/dose) was ca. 1350 mg/kg bw. Clinical symptoms noted were hunched position, dyspnea, aqueous secretion out of the mouth, blood encrusted eyes and noses, horrent fur, spastic gait. All animals were free of symptoms after 4 days (low dose animals recovered quicker). Doses of 0.2, 1.0, 1.25, 1.6, 2.5, 3.2, 6.4 ml/kg were tested. No mortality was observed at 0.2 ml/kg and 1.25 ml/kg; at 1.0 ml/kg 1/10 animals died, at 1.6 ml/kg 6/10 animals died, at 2.5 ml/kg 8/10 animals died. All animals died at dose levels of 3.2 ml/kg and 6.4 ml/kg. Gross necropsy was performed in all animals. The following findings were recorded: Animals that died: blood encrusted eyes, smeared anuses, intestines with test substance smell, inflated stomach, diarrhea. Sacrificed animals at end of study: organs without findings.

Further available limited data indicates an LD50 > 1140 mg/kg (1/5 rats died at this dose level; Gaworski, 1979) and an LD50 of 2250 mg/kg (TSCAT, OTS0571642) both in rats.

Acute inhalation toxicity

This information is not available

Acute dermal toxicity

In an acute dermal toxicity study (Limit Test according to OECD 402 guideline and GLP), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the substance (as suspension in olive oil Ph.Eur.) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

The following test item-related effects were recorded during the course of the study:

· No mortality occurred

· No signs of systemic toxicity

· Very slight to well defined erythema (grade 1 to 2)

· Very slight to slight edema (grade 1 to 2)

· Incrustations

· Scaling

· Yellowish discoloration of the application area

· The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not change during the first post-exposure observation week probably due to the bandage procedure, but increased during the second week within the normal range.

· No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available acute oral and dermal toxicity studies, the substance is classified Acute toxicity oral Cat 4 (according to CLP).