Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 February 2016 to 11 March 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Benzaldehyde, hydroxy-, polymer with phenol
Cas Number:
106466-55-1
Molecular formula:
(C7H6O2.C6H6O)x
IUPAC Name:
Benzaldehyde, hydroxy-, polymer with phenol
Test material form:
solid: flakes
Details on test material:
- Appearance: Red – reddish brown solid flake
- Storage conditions: Controlled room temperature (15-25 ºC, below 70 RH %)

Test animals

Species:
rat
Strain:
other: CRL:(WI) rats
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 10 weeks
- Weight at study initiation: 191-243 days
- Fasting period before study: On the night before treatment, the animals were fasted. The food but not water was withheld during an overnight period. The food was returned 3 hours after the treatment.
- Housing: 3 animals / cage. Cage type: Type II. polypropylene/polycarbonate. Animals were housed by group to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 19-22 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19.3 - 22.8 °C
- Humidity: 30-68 %
- Air changes: 15-20 air exchanges/hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- DMSO Lot/batch no. (if required): SZBE2790V

DOSAGE PREPARATION:
- The powdered test material was freshly formulated at a concentration of 200 or 30 mg/mL in the vehicle on the day of administration. The formulation container was stirred continuously up to finishing the treatment.

CLASS METHOD
- The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
- Initially, three female animals were treated with 2000 mg/kg bw of the test material. One animal died, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As all three animals were found dead in this second dose group, further testing was needed at a dose level of 300 mg/kg bw.
- Three female animals were treated with 300 mg/kg bw of the test material and one animal died in this group, therefore further 3 animals were treated at the same dose level As only one animal died again in the 300 mg/kg bw group, no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris.
Doses:
300 and 2 000 mg/kg bw
No. of animals per sex per dose:
6 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter, where possible. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter, where possible. Terminal body weights of animals found dead were recorded.
- Necropsy of survivors performed: Yes, macroscopic examination was performed on all animals. The surviving animals were sacrificed by exsanguination under pentobarbital anaesthesia. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
Statistics:
The method used was not intended to allow the calculation of a precise LD50 value. The test material was ranked into categories of Globally Harmonised Classification System (GHS (rev. 6) 2015). Clinical signs, body weight, body weight gain and gross macroscopic data were tabulated.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 300 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The test material caused mortality in four of 6 animals at a dose level of 2 000 mg/kg bw and in two of 6 animals at a dose level of 300 mg/kg bw.
Clinical signs:
- Decreased activity and hunched back were observed in all animals (12/12) following treatment with the test material.
- In the groups treated at a dose level of 2 000 mg/kg bw, incoordination (5/6), piloerection (5/6) and prone position (2/6) were also noticed.
- In the groups treated at a dose level of 300 mg/kg bw, incoordination (6/6), piloerection (4/6) and prone position (1/6) were recorded besides the decreased activity and hunched back symptoms. One animal also had decreased respiratory rate just before death.
Body weight:
- The animals that survived the treatment at a dose level of 2 000 mg/kg bw lost weight during the first week, but gained weight during the second week. The surviving animals of the two groups of 300 mg/kg bw treatment gained weight continuously during 14-days observation period.
Gross pathology:
- Reddish cheesy material in the digestive contents of the stomach mixed with diet was found in the rats that died during the observation period; this was considered to be the administered test material.
- No macroscopic findings were noted in the surviving animals dosed at 300 mg/kg bw or 2 000 mg/kg bw and terminated on Day 14.

Any other information on results incl. tables

Table 1: Clinical Observations

Dose Level (mg/kg bw)

Animal No.

Observations

Observation Days

0

1

2

3

4

5

6

7-14

Frequency

30 min

1h

2h

3h

4h

6h

2000

8199

Symptom Free

-

-

-

-

-

-

-

-

+

+

+

+

+

12/20

Activity decreased

1

1

2

2

2

2

1

-

-

-

-

-

-

7/20

Hunched back

+

+

+

+

+

+

+

+

-

-

-

-

-

8/20

Incoordination

-

1

1

1

-

-

-

-

-

-

-

-

-

3/20

Piloerection

-

-

+

+

+

+

+

+

-

-

-

-

-

6/20

8200

Activity decreased

1

1

2

2

2

2

 

 

 

 

 

 

 

6/6

Hunched back

+

+

+

+

+

+

 

 

 

 

 

 

 

6/6

Incoordination

-

2

1

1

-

-

 

 

 

 

 

 

 

3/6

Piloerection

-

-

+

+

+

+

 

 

 

 

 

 

 

4/6

Found Dead

-

-

-

-

-

-

+

 

 

 

 

 

 

-

8201

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

+

14/20

Activity decreased

1

1

2

1

-

-

-

-

-

-

-

-

-

4/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

-

6/20

Incoordination

-

-

1

1

-

-

-

-

-

-

-

-

-

2/20

Piloerection

-

-

+

+

+

+

-

-

-

-

-

-

-

4/20

8202

Activity decreased

1

2

 

 

 

 

 

 

 

 

 

 

 

2/2

Hunched back

+

-

 

 

 

 

 

 

 

 

 

 

 

1/2

Prone Position

-

+

 

 

 

 

 

 

 

 

 

 

 

1/2

Found Dead

-

-

+

 

 

 

 

 

 

 

 

 

 

-

8203

Activity decreased

1

2

2

2

2

2

 

 

 

 

 

 

 

6/6

Hunched back

+

+

+

+

+

+

 

 

 

 

 

 

 

6/6

Incoordination

-

1

2

1

1

1

 

 

 

 

 

 

 

5/6

Piloerection

-

-

+

+

+

+

 

 

 

 

 

 

 

4/6

Found Dead

-

-

-

-

-

-

+

 

 

 

 

 

 

-

8204

Activity decreased

1

2

2

2

2

3

 

 

 

 

 

 

 

6/6

Hunched back

+

+

+

+

+

-

 

 

 

 

 

 

 

5/6

Prone Position

-

-

-

-

-

+

 

 

 

 

 

 

 

1/6

Incoordination

1

1

1

1

1

-

 

 

 

 

 

 

 

5/6

Piloerection

-

-

+

+

+

+

 

 

 

 

 

 

 

4-6

Found Dead

-

-

-

-

-

-

+

 

 

 

 

 

 

-

300

8205

Activity decreased

1

1

1

1

2

3

 

 

 

 

 

 

 

6/6

Hunched back

+

+

+

+

+

-

 

 

 

 

 

 

 

5/6

Prone Position

-

-

-

-

-

+

 

 

 

 

 

 

 

1/6

Incoordination

-

1

1

1

1

-

 

 

 

 

 

 

 

4/6

Piloerection

-

-

+

+

+

+

 

 

 

 

 

 

 

4/6

Respiratory Rate Decreased

-

-

-

-

-

2

 

 

 

 

 

 

 

1/6

Found Dead

-

-

-

-

-

-

+

 

 

 

 

 

 

-

8206

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

+

14/20

Activity Decreased

1

1

1

1

-

-

-

-

-

-

-

-

-

4/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

-

6/20

Incoordination

-

1

-

-

-

-

-

-

-

-

-

-

-

1/20

Piloerection

-

-

-

+

+

-

-

-

-

-

-

-

-

2/20

8207

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

+

14/20

Activity Decreased

1

1

1

1

-

-

-

-

-

-

-

-

-

4/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

-

6/20

Incoordination

-

1

-

-

-

-

-

-

-

-

-

-

-

1/20

8208

Symptom Free

-

-

-

-

-

+

+

+

+

+

+

+

+

15/20

Activity Decreased

1

1

1

-

-

-

-

-

-

-

-

-

-

3/20

Hunched back

+

+

+

+

+

-

-

-

-

-

-

-

-

5/20

Incoordination

-

1

-

-

-

-

-

-

-

-

-

-

-

1/20

8209

Activity decreased

1

1

1

1

2

1

 

 

 

 

 

 

 

6/6

Hunched back

+

+

+

+

+

+

 

 

 

 

 

 

 

6/6

Incoordination

-

1

1

1

1

1

 

 

 

 

 

 

 

5/6

Piloerection

-

-

-

+

+

+

 

 

 

 

 

 

 

3/6

Found Dead

-

-

-

-

-

-

+

 

 

 

 

 

 

-

8210

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

+

14/20

Activity Decreased

1

1

1

1

-

-

-

-

-

-

-

-

-

4/20

Hunched back

+

+

+

+

+

+

-

-

-

-

-

-

-

6/20

Incoordination

-

1

1

-

-

-

-

-

-

-

-

-

-

2/20

Piloerection

-

-

-

+

+

-

-

-

-

-

-

-

-

2/20

 

+ = present, - = absent, Frequency of observation = number of occurrence of observation / total number of observations, Severities: 1 = Slight/Small/Few; 2 = Moderate/Medium; 3 = Marked/Large/Many

Applicant's summary and conclusion

Interpretation of results:
other: EU Criteria: Category 4: Harmful if swallowed (H302).
Conclusions:
Under the conditions of this study, the acute oral LD50 value of the test material was found to be between 300 and 2 000 mg/kg bw in female CRL:(WI) rats.
Executive summary:

The single-dose oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1.Tris and OPPTS 870.1100, under GLP conditions using the acute toxic class method in CRL:(WI) rats.

Two groups of three female CRL:(WI) rats were treated with the test material at a dose level of 2 000 mg/kg bw (Group 1 and Group 2) and two groups of three female CRL:(WI) rats at a dose level of 300 mg/kg bw (Group 3 and Group 4).

A single oral treatment was carried out by gavage for each animal after an overnight food withdrawal. Food was made available again 3 hours after the treatment. The test material was administered formulated in DMSO at a concentration of 200 or 30 mg/mL at a dose volume of 10 mL/kg bw.

Initially, three females (Group 1) were treated at a dose level of 2 000 mg/kg bw. As only one animal was found dead, a confirmatory group (Group 2) was treated at the same dose level. All three animals died in this confirmatory group, therefore the next dose level was 300 mg/kg bw. As only one animal was found dead in the group treated at a dose level of 300 mg/kg bw (Group 3), a confirmatory group (Group 4) was treated at the same dose level. In this group also only one animal died; therefore no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris.

Clinical observations were performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter, where possible. Body weight was measured on Days -1, 0 and 7 and before necropsy. All animals were subjected to a necropsy and a macroscopic examination.

The test material caused mortality in four of 6 animals at a dose level of 2 000 mg/kg bw and in two of 6 animals at a dose level of 300 mg/kg bw.

Decreased activity and hunched back were observed in all animals (12/12) following treatment with the test material. In the groups treated at a dose level of 2 000 mg/kg bw, incoordination (5/6), piloerection (5/6) and prone position (2/6) were also noticed. In the groups treated at a dose level of 300 mg/kg bw, incoordination (6/6), piloerection (4/6) and prone position (1/6) were recorded besides the decreased activity and hunched back symptoms. One animal also had decreased respiratory rate just before death.

The animals that survived the treatment at a dose level of 2 000 mg/kg bw lost weight during the first week, but gained weight during the second week. The surviving animals of the two groups of 300 mg/kg bw treatment gained weight continuously during 14-days observation period.

Reddish cheesy material in the digestive contents of the stomach mixed with diet was found in the rats that died during the observation period; this was considered to be the administered test material. No macroscopic findings were noted in the surviving animals dosed at 300 mg/kg bw or 2 000 mg/kg bw and terminated on Day 14.

Under the conditions of this study, the acute oral LD50 value of the test material was found to be between 300 and 2 000 mg/kg bw in female CRL:(WI) rats.