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Description of key information

Acute oral toxicity in rats: LD 50 > 5000 mg/kg bw

Acute dermal toxicity in rabbits: LD 50 > 5000 mg/kg bw

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:
Jan 21, 1986 - May 16, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: FIFRA (US EPA)
Qualifier:
according to guideline
Guideline:
other: TSCA (US EPA)
GLP compliance:
not specified
Test type:
standard acute method
Species:
rat
Strain:
other: CDR (Sprague-Dawley derived)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Species: Albino rats, CDR (Srague-Dawley derived)
- Source: Charles River Breeding Laboratories, Inc; Wilmington , Massachusetts, USA
- Age at study initiation: Young adults /approx. 9-12 weeks
- Weight at study initiation (prefasted): - Males: 250 - 338 g
- Females: 212 - 269 g
- Fasting period before study: approx. 18 h
- Housing: Group housed (6 per cage) during acclimation, individually during study in suspended stainless steel cages with wire mesh bottoms
- Diet: Purina Laboratory Chow, ad libitum
- Water: ad libitum
- Acclimation period: 8, 10 or 21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 24.5°C (= 67 - 76°F)
- Humidity (%): 30 - 70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Test material was administered by oral intubation, using a ball-tipped intubation needle fitted onto a syringe
Doses:
4000 mg/kg, 5000 mg/kg, 6250 mg/kg
No. of animals per sex per dose:
5 (except 5000 mg/kg dose: 10 male, 5 female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 1 h, 2 h, and 4 h after application; thereafter daily for 14 days
- Frequency of weighing: Pre-fast, post-fast, day 7 and day 14
- Necropsy of survivors performed: yes
- Gross postmortem examinations were performed on all animals which died or were found dead during the study
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
see table below
Clinical signs:
No abnormalities were observed during 4 h after application.
24 h after application and/or day 2 most animals exhibited hypoactivity, soft stool, fecal and/or urinary staining.
All surviving animals were free of significant abnormalities at termination of the study
Body weight:
Most animals exhibited decreased food consumption at 24 h and/on day 2.
Most animals in the 5000 mg/kg group exhibited weight losses at day 7, but gained weight between day 7 and day 14.
The majority of other animals gained weight between both 7 days and 14 days after dosing.
Gross pathology:
Postmortem examinations of animals found dead during the study revealed primarily changes in lungs and gastrointestinal tract.
Several animals exhibited changes in the stomach and intestine which were suggestive of a corrosive effect.
Other changes appeared to represent autolytic changes or antemortem stress.

Dose levels and mortality (excerpt from original report):

Dose level (mg/kg)

Mortality

Male

Female

Total

Time of death (day)

4000

1/5

1/5

2/10

2 - 3

5000 (A)

(4/5) a

1/5

a

2 – 7

5000 (B)

2/5

-

2/5

2 – 4

6250

2/5

1/5

3/10

2 - 3

a: Because the weight of males dosed initially at 5000 mg/kg [designated 5000 (A)] exceeded the weight range of males dosed at the other two levels, an additional group of males in the same weight range as males in the other two dose levels was dosed [(designated 5000 (B)].

Only data from the 5000 (B) group were considered for estimation of LD50.

Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The test substance, alkylation and transalkylation products of biphenyl with propene, showed low toxicity only.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study KLimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

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:
Jan 27, 1986 - Feb 26, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
other: FIFRA (US EPA)
Qualifier:
according to guideline
Guideline:
other: TSCA (US EPA)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Species: New Zealand White, albino rabbits
- Source: Hazleton-Dutchland, Inc., Denver, Pennsylvania
- Age at study initiation: young adult (at least 8 weeks)
- Weight at study initiation: - Males: 2.4 - 2.8 kg
- Females: 2.6 - 2.8 kg
- Housing: individually in suspended stainless steel cages with wire mesh bottoms
- Diet: Lab Rabbit Chow HF, ad libitum:
- Water: ad libitum
- Acclimation period: 16 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 16°C - 21°C (60 - 70°F)
- Humidity (%): 30-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped intact skin of the dorsal area of the trunk
- Application: directly onto the skin and spread evenly over the entire area
- Type of wrap if used: Gauze, impervious plastic sleeve secured by Elizabethan collars


REMOVAL OF TEST SUBSTANCE
Following 24 h of exposure, wrappings were removed and test sites wiped free of excess test material

TEST MATERIAL
- Amount applied: 5.2 ml/kg
- Concentration: undiluted
Duration of exposure:
24 h
Doses:
single dose (5.2 ml/kg = ca. 5000 mg/kg)
No. of animals per sex per dose:
5 per sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 1, 2, and 4 h after application and daily thereafter for 14 days
- Frequency of weighing: Pre-test (at the time of clipping), pre-dose (for calculation of doses), day 7 and day 14
- Necropsy of survivors performed: yes
- Necropsy observations: Lung, ovaries, uterus
Statistics:
not appicable (limit test)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived throughout the study.
Clinical signs:
Few (female) animals exhibited severe dermal effects at the dose site (necrosis followed by eschar formation, fissuring and/or exfoliation of the
eschar tissue) between day 3 and day 9 (see table below).
All animals were free of abnormal signs from day 10 to day 14.
Body weight:
Some animals with decreased food consumption from day 3 to day 7.
Gross pathology:
Gross postmortem observations were similar to those seen in control animals or represent normal physiological variation.

Summary of pharmacologic and toxicologic signs (excerpt from orignal report)

Day

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Hr

1

2

3

4

24

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

M/F

Observation

Food consumption decrease

-

-

-

-

-

-

-

2/2

2/3

1/1

1/2

2/1

-

-

-

-

-

1/-

-

Necrosis

-

-

-

-

-

-

-

-/2

-/2

-/2

-/2

-/2

-/1

-

-

-

-

-

-

Eschar

-

-

-

-

-

-

-

-

-

-/2

-/2

-/2

-/1

-

-

-

-

-

-

Exfoliation

-

-

-

-

-

-

-

-

-

-

-/1

-/2

-/2

-/1

-

-

-

-

-

Fissuring

-

-

-

-

-

-

-

-/1

-/2

-/2

-/2

-

-

-

-

-

-

-

-

M: male, F: female

Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The test substance, alkylation and transalkylation products of biphenyl with propene showed no systemic toxicity after dermal exposure to rabbits.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study KLimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Alkylation and transalkylation products of biphenyl with propene (DIPB/TIPB) produces no acute toxicity but at very high doses.

Mortality was only observed following oral exposure of the neat substance without reaching the LC50 discriminating dose (5000 mg/kg bw).


Justification for selection of acute toxicity – oral endpoint
The high doses selected were lethal in a few cases but did not reach the LD50, and caused intoxication as evidenced by clinical signs and macroscopic observations.

Justification for selection of acute toxicity – dermal endpoint
The limit dose selected was not lethal. However, there was evidence of skin irritation.

Justification for classification or non-classification

According to criteria set in either directive 67/548/EEC or Regulation (EC) No 1272/2008, Alkylation and transalkylation products of biphenyl with propene is not acutely toxic. Classification is not required.