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Administrative data

Description of key information

Acute oral toxicity (OECD 401): LD50 (rat) = 591 mg/kg bw

Acute dermal toxicity (OECD 402): LD50 (rat) not determinable due to the corrosiveness of the test substance

Acute dermal toxicity (similar to OECD 402): LD50 (rat) > 2000 mg/kg bw (RA from 2-phenylphenol, CAS 90-43-7)

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:
17 Feb - 29 Jul 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1988
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Version / remarks:
1984
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: MAFF Acute Oral Toxicity Study
Version / remarks:
1985
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratoris Inc., USA
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: 167.2 - 226.1 g (males) and 120.7 - 143.2 g (females)
- Fasting period before study: Yes, animals were fasted overnight.
- Housing: 2 or 3 animals per cage were housed in animal care facilities.
- Diet: Purina Certified Rodent Chow #5002 (supplied by Purina Mills Inc., USA), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 Feb 1994 To: 29 Jul 1994
Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 and 50%, respectively

DOSAGE PREPARATION: The test substance was administered as a 10 or 50% suspension in 0.5% methocel.
Doses:
100, 500, 1000 and 5000 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: The animals were observed for clinical signs 30 min, 1, 4, 5 and 6 h post-dosing and thereafter at least once each working day throughout the 14-days observation period. The body weight was recorded 1 day before treatment, and thereafter on day 1, 2, 8 and 15.
- Necropsy of survivors performed: Yes, all rats submitted alive to necropsy were anesthetized by inhalation of methoxyflurane vapors and euthanized by decapitation and clamping of trachea.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
591 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
846 mg/kg bw
Based on:
test mat.
Mortality:
5000 mg/kg bw: 5/5 males and 5/5 females died on day 1.
1000 mg/kg bw: 1/5 males and 1/5 females died on day 2. 2/5 males and 3/5 females died on day 5.
500 mg/kg bw: 1/3 males died on day 3 and 2/5 females died on day 5.
Clinical signs:
In-life observations noted were lacrimation, salivation, chromorhinorrhea, labored respiration, decreased activity, lateral recumbency, incoordination, decreased muscle tone, mouth breathing and urine and fecal soiling in the perineal area. Clinical signs began within a half hour of dosing. Most clinical signs resolved during the two-week observation period, although a few signs persisted in one male survivor from the 1000 mg/kg bw dose group and one female survivor from the 500 mg/kg bw dose group, through the 2-week observation period.
For details please refer to Table 1 under "any other information on results incl. tables".
Body weight:
Most surviving rats gained weight during the two-week observation period, with the exception of one female from the 500 mg/kg bw dose group that lost weight, and had a persistence of numerous clinical signs throughout the observation period.
Gross pathology:
The rats that died during the 2-week post-exposure observation period had treatment-related gross pathologic observations consisting of one or more of the following: hemolyzed blood in the digestive tract, perineal soiling, general visceral congestion, decreased amount of fat, pale liver, congested lungs, bloody urine and congestion, erosions and/ or ulcers, hemorrhage, or hyperemia of the stomach. The gross observations of the stomach and digestive tract were consistent with stress-induced alterations. The remaining observations in the animas that died were non-specific signs of toxicity.
There were no treatment-related gross pathologic observations in any of the surviving rats.

Table 1: Clinical signs in males

Time post- dosing   100 mg/kg bw 500 mg/kg bw 1000 mg/kg bw 5000 mg/kg bw
30 min survivors 5 5 5 5
 salivation - 5 4 4
urine soiling - 2 - -
fecal soiling - 1 1 -
decreased activity - - 4 1
incoordinated - - 3 1
decreased muscletone - - 1 3
 laterally recumbent - - 1 3
mouth breathing - - - 2
1 h survivors 5 5 5 4
 salivation - 5 4 3
urine soiling - 1 - -
fecal soiling - 1 - -
decreased activity - 1 4 1
incoordinated - 1 2 1
decreased muscletone - - 1 3
 laterally recumbent - - 1 3
lacrimation - - 1 3
4 h survivors 5 5 5 4
 salivation - 5 4 2
urine soiling - 2 1 1
fecal soiling - 1   -
decreased activity - 1 4 -
incoordinated - 1 3 -
decreased muscletone - - - 3
 laterally recumbent - - - 4
mouth breathing - - 1  
irregular respiration - - - 1
lacrimation - 1 - 4
5 h survivors 5 5 5 1
 salivation - 5 4 -
urine soiling - 3 - -
fecal soiling - 2 - -
decreased activity - 1 4 -
incoordinated - 1 3 -
decreased muscletone - - - 1
 laterally recumbent - - - 1
irregular respiration - - - 1
lacrimation - - - 1
6 h survivors 5 5 5 0
 salivation - 5 4 -
urine soiling - 3 3 -
fecal soiling 1 2 - -
decreased activity - 1 4 -
incoordinated - 1 3 -
mouth breathing - - 1 -
chromorhinorrhea - - 1 -
lacrimation - 1 - -
Day 2 survivors 5 5 4 0
 salivation - 5 3 -
urine soiling - 3 3 -
fecal soiling - 2 - -
decreased activity - 1 3 -
incoordinated - 1 2 -
mouth breathing - - 1 -
chromorhinorrhea - - 1 -
lacrimation - 1 1 -
Day 5 survivors 5 4 2 0
 salivation - - 1 -
urine soiling - 1 1 -
fecal soiling - 1 - -
decreased activity - - 1 -
Day 6 survivors 5 4 2 0
 salivation - - 1 -
urine soiling - - 1 -
fecal soiling - 1 - -
decreased activity - - 1 -
Day 7 survivors 5 4 2 0
urine soiling - - 1 -
fecal soiling - 1 1 -
Day 8 + 9 + 12 survivors 5 4 2 0
urine soiling - - 1 -
Day 13 + 14 + 15 survivors 5 4 2 0
fecal soiling - - 1 -

Table 2: Clinical signs in females

Time post- dosing   100 mg/kg bw 500 mg/kg bw 1000 mg/kg bw 5000 mg/kg bw
30 min survivors 5 5 5 5
 salivation - 5 5 5
urine soiling - - 2 -
fecal soiling - - 2 1
decreased activity - 1 4 2
incoordinated - - 4 2
decreased muscletone - - 1 3
 laterally recumbent - - 1 3
lacrimation - - 2 3
1 h survivors 5 5 5 2
 salivation - 5 5 2
urine soiling - - 2 -
fecal soiling - - 2 -
decreased activity - 1 4 -
incoordinated - - 4 -
decreased muscletone - - 1 2
 laterally recumbent - - 1 1
lacrimation - 1 1 1
4 h survivors 5 5 5 1
 salivation - 5 5 1
urine soiling - 3 2 -
fecal soiling - - 2 -
decreased activity - 1 4 -
incoordinated - 1 4 -
decreased muscletone - - 1 1
 laterally recumbent - - 1 1
lacrimation - 2 3 1
5 h survivors 5 5 5 1
 salivation - 5 5 1
urine soiling - 3 2 -
fecal soiling - - 2 -
decreased activity - 1 4 -
incoordinated - 1 4 -
decreased muscletone - - 1 1
 laterally recumbent - - 1 1
chromorhinorrhea - 1 - -
lacrimation - 2 2 1
6 h survivors 5 5 5 1
 salivation - 4 5 1
urine soiling - 4 2 -
fecal soiling - - 2 -
decreased activity - 3 4 -
incoordinated - 3 4 -
decreased muscletone - - 1 1
chromorhinorrhea - 1 - -
lacrimation - 1 2 1
Day 2 survivors 5 5 4 0
 salivation - 4 4 -
urine soiling - 4 4 -
decreased activity - 3 4 -
incoordinated - 2 2 -
chromorhinorrhea - 2 1 -
lacrimation - 2 1 -
Day 5 + 6 survivors 5 3 1 0
 salivation - 2 1 -
urine soiling - 2 1 -
incoordinated - - - -
decreased activity - 1    
Day 7 + 8 survivors 5 3 1 0
decreased activity - 1 - -
salivation - 2 - -
urine soiling - 2 1 -
fecal soiling - 1   -
Day 9 survivors 5 3 1 0
salivation - 2 - -
fecal soiling - 1 - -
decreased activity - 1 - -
urine soiling - 1 1  
Day 12 survivors 5 3 1 0
salivation - 2 - -
fecal soiling - 1 - -
decreased activity - 1 - -
chromorhinorrhea - 1 - -
labored respiration - 1 - -
urine soiling - 1 - -
Day 13 survivors 5 3 1 0
salivation - 1 - -
fecal soiling - 1 - -
decreased activity - 1 - -
chromorhinorrhea - 1 - -
labored respiration - 1 - -
urine soiling - 1 - -
Day 14 survivors 5 3 1 0
salivation - 1 - -
fecal soiling - 1 - -
decreased activity - 1 - -
labored respiration - 1 - -
urine soiling - 1 - -
Day 15 survivors 5 3 1 0
salivation - 1 - -
fecal soiling - 1 - -
decreased activity - 1 - -
labored respiration - 1 - -
thin - 1 - -
urine soiling - 1 - -
Interpretation of results:
other: Acute oral 4, H302 according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: Acute oral 4, H302
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
591 mg/kg bw
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 1 and 2) and consistent studies, 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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose for cross-reference:
other:
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: not classified

The dermal LD50 value determined in an acute dermal toxicity study with the analogue substance was > 2000 mg/kg bw, because no mortality was observed. Applying the RA-approach, similar results are expected for the registered substance.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information refers to an adequate and reliable guideline study conducted with the analogue substance 2-phenylphenol (CAS 90-43-7), 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

There are suitable and reliable data available regarding acute oral toxicity and acute dermal toxicity for sodium 2-biphenylate (CAS 132-27-4) in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII-VIII, 8.5.

 

Acute oral toxicity

A reliable acute oral toxicity study was conducted with sodium 2-biphenylate (CAS 132-27-4) according to OECD guideline 401 and GLP conditions (Gilbert, 1994). Five male and five female Fischer 344 rats each received a single oral gavage dose of 100, 500, 1000 and 5000 mg/kg bw of the test substance in methylcellulose. The animals were observed for 14 days after administration. At 100 mg/kg bw, no mortality and no clinical signs occurred. At 500 mg/kg bw, 1/5 males died on day 3 and 2/5 females died on day 5, whereas at 1000 mg/kg bw 1/5 males and 1/5 females died on day 2 and 2/5 males and 3/5 females died on day 5, respectively. At the highest dose level, all males and females died on day 1. The clinical signs observed include lacrimation, salivation, chromorhinorrhea, labored respiration, decreased activity, lateral recumbency, incoordination, decreased muscle tone, mouth breathing and urine and fecal soiling in the perineal area. Based on these results, the acute oral LD50 was found to be 591 mg/kg bw in females and 846 mg/kg bw in males, respectively.

A non-GLP conform performed with sodium 2-biphenylate (CAS 132-27-4) and similar to OECD guideline 401 was used as supporting information (Löser, 1980). Groups of 5 male and 5 female Wistar rats received a single oral gavage dose of 1000, 1300, 1500, 2000, 2200 and 2500 mg/kg bw of the test substance in water. Only at the lowest dose level mortality did not occur. At the dose levels 1300 – 2500 mg/kg bw mortality, narcosis and a decline in general conditions in both sexes occurred. At the highest dose level all males and females died.The clinical signs occurred 1 h after treatment and persisted up to day 5 at the dose levels 1300, 1500 and 2000 mg/kg bw, and up to the end of the 14-day observation period at the dose level of 2200 mg/kg bw. Weight loss was observed starting from doses of 2200 to 2500 mg/kg bw. Based on the results of the present study a LD50 value of 1720 mg/kg bw was derived for males and females.

 

Acute dermal toxicity

An acute dermal toxicity study (limit test) was performed with sodium 2-biphenylate (CAS 132-27-4) according to OECD guideline 402 and GLP conditions (Busschers, 1997). Five male and five female Wistar rats were exposed to 2000 mg test substance /kg bw in water for 24 h on the dorsal area of trunk under occlusive conditions. The observation period was 14 days. 1/5 males were found dead and 4/5 males were sacrificed for humane reasons on day 5 after dosing. 4/5 females and 1/5 females were sacrificed for humane reasons on day 2 and 5 after dosing, respectively, due to severe necrosis and body weight losses. Thus, because of severe necrosis, except for one male, all animals were sacrificed in extremis within 5 days following treatment , and consequently, no LD50 value could be assessed within this study. Therefore, read-across data were needed and for this purpose, the analogue substance 2-phenylphenol CAS 90-43-7 (for justification, please refer to Section 13) was considered as source.

An acute dermal toxicity study with rat is available for the analogue substance 2-phenylphenol (OPP) (Bomhard, E., 1991 and Bomhard, E. M. et al., 2002). The methods complied with the guideline 84/449/EEC (Gazette of the European Community, No. L 251, p. 103) and was comparable to the OECD Guideline 402. The test item was applied dermally to young-adult male and female Wistar rats. Five rats were used per sex. The study was performed as a limit test using 2000 mg/kg body weight. The test substance was prepared as a paste using several drops of Cremophor E and applied semi-occlusively to the shaved skin of the animals (approximately 10% of body surface). The dressing was removed after 24 h and residual test substance was removed with luke-warm water. The animals were inspected several times on the day of administration and twice daily during the 14-day observation period (once on weekends and holidays). During inspections, type, onset, duration, and intensity of clinical signs were recorded; dead animals were removed if necessary. The animals were weighed individually directly before administration (day 1), after one week and at the end of the 14-day observation period. Gross pathological examinations were performed on all animals at the end of the study. No deaths resulted from the treatment at the dermal limit dose, therefore, additional dose levels were not tested and LD50 values were not determined. Only a slight reddening of the application site was observed on all animals on the day after application. This reddening became incrusted on the 5th day after application and was resolved at the end of the observation period. Body weight gain was only affected in 3 female rats during the first week after application, but all affected animals had surpassed their initial body weights at study termination again. No treatment-related gross lesions were noticed at necropsy. The dermal LD50 value for the analogue substance OPP was >2000 mg/kg bw.

Applying the RA-approach, the LD50 for acute dermal toxicity is > 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute oral toxicity with sodium 2-biphenylate (CAS 132-27-4) meet the classification criteria as Acute oral 4, H302 according to Regulation (EC) No. 1272/2008. Applying the RA-approach, the available data on acute dermal toxicity do not meet the classification criteria according to Regulation No. (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

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