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Administrative data

Description of key information

Terphenyl, hydrogenated was very well tolerated after acute oral, inhalation and dermal dosing. LD50 values were systematically above the limit doses, therefore the test material is considered to be safe from an acute toxicity viewpoint.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: In compliance with 21 CFR Part 58, available as unpublished report, no restrictions, adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Remarks:
in compliance with 21 CFR Part 58 (FDA GLP)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles river.
- Age at study initiation: Approximately 8 weeks (young adults).
- Weight at study initiation: 261-290 grams (males), 177-204 grams (females).
- Fasting period before study: Animals were fasted overnight prior to test material administration.
- Housing: One per cage.
- Diet (e.g. ad libitum): ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: Animals quarantined for at least one week.
- Each animal was individually ear tagged. Animals randomly assign to this study.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10000 mg/kg

Doses:
Single dose: 10000 mg/kg
No. of animals per sex per dose:
A single group of 5 Males, 5 Females /dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Twice daily examinations were made for mortality and signs of toxicity.
Body weights were recorded on the first day of testing and weekly thereafter.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
No deaths were seen in animals of either sex.
Clinical signs:
Hypoactivity, diarrhea, feces-stained fur, and urine-stained fur were observations considered to be effects of the test materials.
Gross pathology:
No abnormalities
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
LD50 > 10.000 mg/kg
Executive summary:

No deaths resulted from an oral dosage of 10.000 mg/kg body weight of Terphenyl, hydrogenated to fasted albino rats of both sexes (approximately 8 weeks old). Therefore LD50 is considered to be higher than 10.000 mg/kg body weight. Observations included hypoactivity, diarrhea, faeces-stained fur and urine-stained fur.

Endpoint conclusion
Dose descriptor:
LD50
Value:
12 500 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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant study, available as unpublished report, no restrictions, adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: Approximately 5 weeks
- Weight at study initiation: 127-185 grams (males), 101-141 grams (females)
- Housing: Individually housed (during the exposure)
- Diet (e.g. ad libitum): ad libitum (except during the exposure period)
- Water (e.g. ad libitum): ad libitum (except during the exposure period)
- Acclimation period: Test animals were held and observed in quarantine for 10 days prior to release for study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 70-74°F
- Humidity (%): 39-70% relative humidity
- Air changes (per hr): 19.2 to 22.2 liters/min
- Photoperiod: 12 hrs dark / 12 hrs light cycle

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Laskin-type nebulizer
- Exposure chamber volume: 0.3 m³
- Method of holding animals in test chamber: One par cage, positioned in two tiers in the chamber
- Method of particle size determination: Andersen cascade impactor

TEST ATMOSPHERE
- Brief description of analytical method used: Determinated by gas chromatography
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 92.9-95.8% of particles were less than 10um in size
- MMAD (Mass median aerodynamic diameter): 1.82-2.36um
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gas chromatography
Duration of exposure:
4 h
Remarks on duration:
single exposure
Concentrations:
2.5 mg/L; 3.6 mg/L; 4.4 mg/L; 4.7 mg/L
No. of animals per sex per dose:
6 Males ,6 Females /exposure concentration
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of the external appearance and of tissues of the thoracic, abdominal and cranial cavities.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.7 mg/L air
Exp. duration:
4 h
Mortality:
At 4.7 mg/L: 5 rats died (1 males, 4 females) on a total of 36 animals
Clinical signs:
other: In treated animals immediately after exposure were observed: salivation increase; wet fur on the ventral side (due to salivation); discharge and/or encrustation about the nose and eyes; labored breathing; prostrate condition and fur coated with test mater
Body weight:
At 3.6-4.7 mg/L: decreases in mean body weights.
Gross pathology:
Not test-related
Other findings:
All of the effects noted above were reversible by the end of the study (day 14)
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
LC50 > 4.7 mg/L
Executive summary:

Six groups of 6 male and 6 female Sprague-Dawley rats per group were each exposed once for 4 hours to atmospheres of aerosolized hydrogenated terphenyl. Mean exposure concentrations ranged from 2,5 to 4.7 mg of Terphenyl, hydrogenated vapor/aerosol per liter of air. The chamber atmospheres were run at elevated and ambient temperatures. Two groups of rats were exposed to house-conditioned air and served as ambient and heated control groups. Exposures were followed by a 14-day observation period and subsequent necropsy. The LC50 for the material could not be calculated due to the low incidence of mortality (3 out of 12 in a single exposure at 4.7 mg/L). In treated animals immediately after exposure, notable observations included salivation, wet fur on the ventral side (due to salivation), discharges and/or encrustation about the nose and eyes, labored breathing, prostrate condition and fur coated with test material. Post-exposure observations included red encrustation about eyes and nose, fur coated with test material and labored breathing. By post-exposure day 14 all surviving animals were in apparent good health. Decreases in mean body weights were noted by post-exposure day 2 in all groups except in the lowest exposure concentration (ambient) and control groups. By the end of the 14 day post-exposure period all groups had exceeded their pre-exposure weights. There were no terminal necropsy findings which are considered to be related to the test material. Based on the test exposure results, the LC50 value for Terphenyl, hydrogenated administered in the study is considered to be greater than 4.7 mg/L.

Endpoint conclusion
Dose descriptor:
LC50
Value:
4 700 mg/m³

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: In compliance with 21 CFR Part 58, available as unpublished report, no restrictions, adequate for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Isaac's farm
- Age at study initiation: Approximately 10 weeks
- Weight at study initiation: 2.25-2.86 kg
- Housing: One per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Shaved dorsal surface
- Type of wrap if used: latex rubber dantal dam


Duration of exposure:
24 hours (continuous)
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 Males, 5 Females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: three times during the first 8h and twice daily thereafter for a total of 14 days on test.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths in either sex
Body weight:
No abnormal physical observations were noted during this study.
Gross pathology:
No abnormalities were observed at gross necropsy.
Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
LD50 > 2.000 mg/kg
Executive summary:

No deaths resulted from a dermal (24h occlusive) dosage of 2.000 mg/kg body weight of Terphenyl, hydrogenated to the shaved dorsal surface of of 5 male and 5 female New Zealand albino rabbits of both sexes. LD50 was therefore higher than 2.000 mg/kg body weight. No treatment-related abnormalities were noted in any groups.

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

A key study for acute oral toxicity was performed according to OECD 401 and GLP testing guidelines and was therefore considered to be reliable, relevant and adequate. No deaths resulted from an oral dosage of 10.000 mg/kg body weight of hydrogenated terphenyl to fasted male and female albino rats (Branch et al., 1980 – Monsanto study). LD50 was therefore higher than 10.000 mg/kg. Observations included hypoactivity, diarrhea, faeces-stained fur and urine-stained fur. Addition supporting studies ( Klimisch scores 3-4) provided following results: - hydrogenated terphenyl: >24.000 mg/kg in female rats (Clarck et al., 1979 – Literature) - Unknown composition: 17.500 mg/kg in male rats (Adamson and Weeks, 1973 – Literature) - Unknown composition: 12.500 mg/kg in male mice (Adamson and Weeks, 1973 – Literature) - hydrogenated terphenyl: 10.200 mg/kg in male and female rats (Monsanto, 1970 –IBT study). The latter study was not taken into account as IBT studies are considered to be unreliable unless otherwise stated (OECD-HPV manual on data quality). In conclusion, LD50 was systematically above the limit dose of 2.000 mg/kg body weight.

 

A key study for acute inhalation toxicity was performed according to OECD 403 and GLP testing guidelines and was therefore considered to be reliable, relevant and adequate. Rats were each exposed once for 4 hours to atmospheres of aerosolized hydrogenated terphenyl at mean exposure concentrations ranged from 2.5 to 4.7 mg/L air of hydrogenated terphenyl vapor/aerosol (Bechtel, 1966 – Monsanto study). Mortality was observed in 3 out of 12 rats at 4.7 mg/L. Observations included salivation, wet fur, discharges and/or encrustation about the nose and eyes, labored breathing, prostrate condition and fur coated with test material. By post-exposure day 14 all surviving animals were in apparent good health. There were no test material related terminal necropsy findings. The LC50 was greater than 4.7 mg/L. Another study was further available in rats exposed up to 11.1 mg/L air of aerosolized (Monsanto, IBT report, 1975). As described in the OECD-HPV manual on data quality, IBT studies are considered to be unreliable unless otherwise stated. Finally, another study was performed (Monsanto), however when concentration of test material in the air was determined gravimetrically and indicated that the animals were not exposed to test material during the exposure period. As a consequence the LC50 could not be determined. Therefore these studies were not taken further into account for safety assessment. In conclusion, based on the key study, LC50 was considered to be above the limit concentration of 5 mg/L air.

 

A key study for acute dermal toxicity was performed according to OECD testing guidelines and was therefore considered to be reliable, relevant and adequate. No deaths resulted from a dermal (24h occlusive) dosage of 2.000 mg/kg body weight of hydrogenated terphenyl to the shaved dorsal surface of 5 male and 5 female New Zealand albino rabbits of both sexes (Chow, 1979 – Monsanto study). LD50 was therefore higher than 2.000 mg/kg body weight. No treatment-related abnormalities were noted in any groups. Another study for acute dermal toxicity with hydrogenated terphenyl (Klimisch rating 3) was performed in 2 rabbits/sex/dose at doses up to 10.2 g/kg body weight (Monsanto, 1970 – IBT study). As described in the OECD-HPV manual on data quality, IBT studies are considered to be unreliable unless otherwise stated. Therefore this study was not taken further into account for safety assessment. In conclusion, LD50 was systematically above the limit dose of 2.000 mg/kg body weight.

Justification for classification or non-classification

As LD50 values were above limit doses, there is no need for classification.