A mixture of branched and linear C7-C9 alkyl 3-[3-(2H-benzotriazol-2-yl)-5-(1,1-dimethylethyl)-4-hydroxyphenyl]propionates

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg (male/female), OECD Guideline Study, Ciba-Geigy, 1990
Dermal: LD50 > 2000 mg/kg (male/female), OECD Guideline Study, Ciba-Geigy, 1990

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:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Remarks:

Experimental Toxicology CIBA-GEIGY Limited 4332 Stein / Switzerland

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: 172 to 215 g
- Fasting period before study: overnight
- Housing: 5/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 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
- Frequency of observations and weighing: daily for 14 days, weighing: immediately before administration and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred in this study.

Clinical signs:

other: Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 4 days.

Gross pathology:

At autopsy, a small testis was found in one male. No deviations from normal morphology were found in the remaining animals.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

The oral LD50 value of the test article in rats was found to exceed 2000 mg/kg body weight.

Executive summary:

In a GLP-compliant oral toxicity study according to OECD guideline 401, five male and five female Tif:RAI rats were dosed once with the test article in arachis oil by gastric intubation at a dose level of 2000 mg/kg body weight and observed for 14 days. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortalities were recorded. Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests.

The animals recovered within 4 days. At autopsy, a small testis was found in one male. The body weight gain shown by the animals over the study period was considered to be normal. The oral LD50 value of the test article in rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From Oct. 19, 1987 to Jan. 22, 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study conducted according to GLP. A default reliability of 2 is assigned because of use as read-across

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(1981)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain as stated in the report: Tif:RAI f (SPF) hybrids of RII/1 x RII/2
- Source: CIBA-Geigy Ltd. Animal Production, 4332 Stein Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 195 to 234 g
- Housing: group housed (5 per cage) in Macrolon cages, type 4
- Diet ad libitum: rat chow (NAFAG 890 tox)
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: ethanol

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The exposure apparatus was a nose-only exposure system developed by Battelle Research Centres (Geneve/Switzerland). The internal chamber volume was less than 1 l. The flow in any individual aerosol delivery tube was 2 l/min (velocity 1.25 m/sec) and the total flow was 32 l/min. The aerosol was generated using 2 pneumatic nebulizers in parallel.

- Method of holding animals in test chamber:
The rats were placed in macrolon animal holders during exposure.

- Treatment of exhaust air:
The exhaust air was decontaminated by passage through a Pall HDC absolute filter.

TEST ATMOSPHERE
The aerosol concentration in the chamber was determined gravimetrically 5 times during the exposure period. In the same time interval temperature, relative humidity and oxygen content of the inhalation chamber were assessed. The particle size was analyzed with an aerodynamic particle sizer, equipped with appropriate dilution systems to avoid coincidence counts.

VEHICLE
The test article was too viscous to be directly aerosolized. Preliminary experiments showed that a dilution with absolute ethanol (End concentration 30%) was suitable to generate an appropriate concentration in the inhalation atmosphere.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

determined gravimetrically 5 times during exposure period

Duration of exposure:

4 h

Concentrations:

nominal; 11672 mg/m3
measured; 5838 +/- 151 mg/m3

No. of animals per sex per dose:

5 males, 5 females

Control animals:

yes

Details on study design:

The control animals were treated with 61.8 g/h absolute ethanol (nominal concentration of 32.2 g/m3).
During exposure the animals were examined for clinical symptoms and mortalities at 1, 2, and 4 h, as well as 2 h after the exposure and daily thereafter for 14 days. Body weights were recorded immediately prior to exposure and on days 7 and 14 of the observation period. Gross pathological examinations were performed on all animals at day 14.

Statistics:

Inhalation LC50 values and their 95% confidence limits were not calculated because there were no mortalities. The body weights of the treated animals and the controls were compared by analysis of variance.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.8 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: None of the animals died.

Mortality:

None of the animals died.

Clinical signs:

other: Ruffled fur, dyspnea, hunched posture and reduced spontaneous activity were seen in animals exposed to test material. They recovered within 6 days.

Body weight:

Males exposed to the test article showed a statistically significant higher body weight gain compared to controls during the first week after exposure.

Gross pathology:

No treatment related macroscopic findings were observed.

Other findings:

None

Table 1: Mean body weights in gram (Dose level: 5.8 mg/l)

Test day	0	7	14
Control males	223 +/- 8	258 +/- 9	301 +/- 10
Treated males	232 +/- 2	273 +/- 4 *	314 +/- 9
Control females	206 +/- 7	218 +/- 10	236 +/- 16
Treated females	208 +/- 9	222 +/- 18	239 +/- 22

Body weights on day 0 were assessed before application of test article.

* p<0.05 versus control

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5.8 mg/m³ air

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:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline and GLP compliant study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Remarks:

Experimental Toxicology CIBA-GEIGY Limited 4332 Stein / Switzerland

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: (Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 206 to 256 g
- Fasting period before study: no
- Housing: single
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: about 10%
- Type of wrap if used: gauze-lined semiocclusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was cleaned with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg bw
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: daily; weighing: immediately before application and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred in this study.

Clinical signs:

other: Piloerection, abnormal body positions, and dyspnea were seen, being common symptoms in acute dermal tests. The animals recovered within 5 days.

Gross pathology:

At autopsy, no deviations from normal morphology were found.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

The dermal LD50 value of the test article in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The acute dermal toxicity of the test substance was assessed in a toxicity study following OECD guideline 402 and in compliance with GLP. The test article was administered to five Tif: RAI f rats of each sex by dermal application at 2000 mg/kg body weight. After an exposure period of 24 hours the dressing was removed and the skin was cleaned with lukewarm water. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. Piloerection, abnormal body positions, and dyspnea were seen, being common symptoms in acute dermal tests. The animals recovered within 5 days. Body weight gain was normal throughout the study period. At autopsy, no deviations from normal morphology were found. The dermal LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Oral: In a GLP-compliant acute oral toxicity study (OECD 401, Ciba-Geigy, 904252), two groups of fasted 6-8 week old rats (5/sex) were given a single oral dose of the test item in arachis oil at 2000 mg/kg body weight and observed for 14 days. No mortality occurred and body weight gain was found to be normal. Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 4 days. At autopsy, a small testis was found in one male. No deviations from normal morphology were found in the remaining animals. Oral LD50 of male and female is greater than 2000 mg/kg bw. The test substance is of low toxicity based on the LD50 in males and females.

Dermal: In a GLP-compliant acute dermal toxicity study (OECD 402, Ciba-Geigy, 904255), two groups of 7 - 8 week old rats (5/sex) were dermally exposed to undiluted test material for 24 hours to 10% of body surface area at 2000 mg/kg body weight followed by an observation period of 14 days. No mortality occurred and normal body weight gain were found in this study. Piloerection, abnormal body positions and dyspnea were seen, being common symptoms in acute dermal tests. The animals recovered within 5 days. At autopsy, no deviations from normal morphology were found. Dermal LD 50 of male and female is greater than 2000 mg/kg body weight. The test substance is of low toxicity based on the LD50 of males and females.

Inhalation: The structurally related ester (EC 400 -830 -7) caused no mortality in an acute inhalation study (OECD 403, GLP) with aerosol.

Justification for selection of acute toxicity – oral endpoint
GLP-compliant guideline study

Justification for selection of acute toxicity – dermal endpoint
GLP-compliant guideline study

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC): The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute oral, inhalation or dermal toxicity under Directive 67/548/EEC.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008: The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral, inhalation or dermal toxicity under Regulation (EC) No. 1272/2008.