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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 28 - August 17, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with OECD & EU test guidelines in compliance with GLP and reported with a GLP certificate.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2'-methylenebis[6-(1-methylcyclohexyl)-p-cresol]
EC Number:
201-044-5
EC Name:
2,2'-methylenebis[6-(1-methylcyclohexyl)-p-cresol]
Cas Number:
77-62-3
Molecular formula:
C29H40O2
IUPAC Name:
2-{[2-hydroxy-5-methyl-3-(1-methylcyclohexyl)phenyl]methyl}-4-methyl-6-(1-methylcyclohexyl)phenol
Test material form:
other: solid
Details on test material:
Name: Mutterlaugenrükstand
Batch No.: Fil-1248
Chemical name: not specified by the sponsor
Physical state: brownish sticky solid substance
Density: 1.04 g/ml
Identification: labelled, where appropriate, with name of test article, batch no., name of sponsor, project no., date of receipt, storage conditions, handling precautions and expiry date
Storage: ambient
Stability: not specified by the sponsor

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: rat
Strain: Bor: WISW (SPF Cpb)
Source: Fa. Winkelmann, Versuchstierzucht GmbH & Co. KG, Gartenstr.27, 33178 Borchen
Date of receipt: July 14, 1993 (range finding); July 21, 1993 (main test)
Acclimatization period: 14 days (range finding); 13 days (main test)
Animal selection: random
Animal identification: with colored markings; cage labelled with dosage, sex, date of study initiation, project no.
Weight range at study initiation: m: 196 - 225 g, f: 158 - 187 g

Husbandry
Housing: collective housing up to a maximum of 5 animals per cage (Makrolon® type II)
Illumination: artificial lighting (120 lux) from 7.00 a.m. - 7.00 p.m.
Temperature: 22 ± 3°C
Relative humidity: 30 - 70 %
Measurement: with thermohygrometer twice daily

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
Solvent/vehicle: polyethylene glycol 400 (PEG 400)
Batch: 110. 297833690

The test article was administered as a 20% solution in PEG 400 in a volume of 10 ml/kg. The dissolution of the test substance was performed by stirring and mild warming.
Doses:
Single does 2000 mg/kg bw
No. of animals per sex per dose:
2 females for range finding study
10 animals in the main study (5 males & 5 females)
Control animals:
no
Details on study design:
Pre-experimental procedure
Prior to study initiation, the animals were acclimatized to laboratory conditions for 14 days (range finding) and 13 days (main test). Only healthy animals were used in the test.
The animals were fasted from 16 h before until 3 - 4 h after administration of the test article.

Administration of the test article
A single oral administration of the test article was performed by gavage using a stomach tube.

Range finding
A preliminary range finding test with a dose of 2000 mg/kg body weight was conducted using two female rats.

Main study
Clinical observations
In each animal a number of clinical-toxicological signs were evaluated according to a modified Irwin-Screening procedure (Screening Methods in Pharmacology, R. A. Turner, 1965, p. 26). Any change from the normal condition was noted (increase or decrease) and the degree of severity of any clinical symptoms was assessed. The animals were examined at the following post-treatment intervals: 10 min, 1 h, 2 h, 6 h, 24 h, and thereafter once daily up to day 14.

Body weights
Body weights were recorded immediately before treatment (day 0) and on days 7 and
14 p.a. (termination).

Necropsy
The animals were sacrificed by CO2 asphyxiation after 14 days and gross pathological examinations were subsequently performed.
Statistics:
None specified in the study report.

Results and discussion

Preliminary study:
There were no death in the preliminary study.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died during the course of the main study.
Clinical signs:
No abnormal clinical signs were observed apart from a slight diarrhoea in 9 animals at 6h post administration. The situation resolved itself within 24h.
Body weight:
Weight gains were normal in all animals.
Gross pathology:
Gross pathological examinations at 14 days p. a. (terminal necropsy) revealed no test article-dependent findings. The macroscopic change that was observed was attributable to minor variations which can occur spontaneously in rats of ths strain and age.
Other findings:
No further findings reported in the study.

Any other information on results incl. tables

INDIVIDUAL DOSE AND PRE-TERMINAL DEATHS – RANGE FINDING

Test article: Mutterlaugenrückstand               Project No.: 10-04-0063/00-93

Species: Rat                                            Animal no.: 6 + 7

Sex: f

Anim. No.

Sex

Dose (mg/kg)

Volume (ml)

Pre-terminal deaths

24h

48h

Days p.a.

3

4

5

6

7

8

9

10

11

12

13

14

6

F

2000

1.7

 

 

 

 

 

 

 

 

 

 

 

 

 

 

7

F

2000

1.9

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Open boxes: no pre-terminal deaths

 

INDIVIDUAL DOSE AND PRE-TERMINAL DEATHS – MAIN STUDY

Test article: Mutterlaugenrückstand               Project No.: 10-04-0063/00-93

Species: Rat                                           Animal no.: 1 - 10

Sex: m, f

Anim. No.

Sex

Dose (mg/kg)

Volume (ml)

Pre-terminal deaths

24h

48h

Days p.a.

3

4

5

6

7

8

9

10

11

12

13

14

1

M

2000

2.1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2

M

2000

2.2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

3

M

2000

2.1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

4

M

2000

2.0

 

 

 

 

 

 

 

 

 

 

 

 

 

 

5

M

2000

2.3

 

 

 

 

 

 

 

 

 

 

 

 

 

 

6

F

2000

1.7

 

 

 

 

 

 

 

 

 

 

 

 

 

 

7

F

2000

1.9

 

 

 

 

 

 

 

 

 

 

 

 

 

 

8

F

2000

1.8

 

 

 

 

 

 

 

 

 

 

 

 

 

 

9

F

2000

1.6

 

 

 

 

 

 

 

 

 

 

 

 

 

 

10

F

2000

1.7

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Open boxes: no pre-terminal deaths

 

CLINICAL OBSERVATIONS

Test article: Mutterlaugenrückstand               Project No.: 10-04-0063/00-93

Species: Rat                                           Sex: m,f

Dose mg/kg

Observation period p.a.

Findings

2000

10 min – 2h (10/10)

6h (10/10)

24h – day 14 (10/10)

No abnormal clinical signs

Slight diarrhea in 9 animals

No abnormal clinical signs

Figures in parenthesis indicate number of surviving animals

 

BODY WEIGHTS – INDIVIDUAL VALUES (g)

Dose: 2000 mg/kg

Anim. No.

Sex

Day 0

Day 7 p.a.

Day 14 p.a.

1

M

205

252

274

2

M

218

270

288

3

M

206

252

287

4

M

196

232

257

5

M

225

272

304

6

F

172

191

198

7

F

187

211

217

8

F

178

200

211

9

F

158

176

189

10

F

168

192

207

 

BODY-WEIGHTS – MEAN VALUES (g)

Sex

N

Day 0

Day 7 p.a.

Day 14 p.a.

Males

5

210.0 ± 11.5

255.6 ± 16.3

282.0 ± 17.6

Females

5

172.6 ± 10.9

194.0 ± 12.9

204.4 ± 11.0

 

NECROPSY

Test article: Mutterlaugenrückstand               Project No.: 10-04-0063/00-93

Species: Rat                                           Animal no.: 1 - 10

Sex: m, f                                                Dose: 2000 mg/kg

 

Spontaneous death: ----     n = -

Killed in extremis: ----        n = -

Animal No.

Specified Findings

 

 

 

Terminal sacrifice: 14 days p.a.        n = 10

Animal No.

Specified Findings

7

1 – 6, 8 – 10

Uterus: hydrometra

No specific findings

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
the basis of the results obtaned after a single oral administration, the LD50 values after 24 h and 14 days were as follows:
male and female > 2000 mg/kg
Executive summary:

The aim of the test was to determine the acute median lethal dose of "Mutterlaugenrückstand". Information derived from this test serves to indicate the existence of possible hazards likely to arise from short-term exposure to the test article by the oral route.

The test was conducted according to the OECD guideline for the testing of chemicals OECD 401 (February 24, 1987) and the EEC directive 92/69ÆEC (July 31, 1992). The study was carried out as described in the corresponding protocol approved by the testing facility and the study sponsor on June 28 and July 1, 1993, respectively. The principles of Good Laboratory Practice for the testing of chemicals as specified by national (BGBL. I, no. 13, § 19 a, March 22, 1990) and international (OECD, Paris, 1982) legislation were followed during the performance of the study.

 

SUMMARY

The acute oral toxicity of "Mutterlaugenrückstand" was investigated in 5 male and 5 female Wistar rats.

On the basis of the range finding results, the animals were given a single oral administration of "Mutterlaugenrückstand" at a dose of 2000 mg/kg.

Clinical observations were conducted at regular intervals during the 14-day observation period. Body weights were measured at days 0, 7 and 14 p.a. Gross pathological examinations were performed on all animals 14 days p.a.

 

The following results were obtained:

1. No abnormal clinical signs were observed apart from a slight diarrhea in 9 animals at 6 h p.a.

2. Weight gains were normal in all animals.

3. Gross pathological examinations at 14 days p.a. (terminal necropsy) revealed no test article-dependent findings.

4. On the basis of the results obtained after a single oral administration, the LD50 values after 24 hand 14 days were as follows:

male and female > 2000 mg/kg