Reaction product of salicylaldehyde and formaldehyde and phenol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 September 2012 to 11 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction product of salicylaldehyde and formaldehyde and phenol

EC Number:

632-556-0

Cas Number:

304859-44-7

Molecular formula:

C6H5O(C13H10O2)m(C7H6O)nH values on m and n are variable as this is a UVCB substance

IUPAC Name:

Reaction product of salicylaldehyde and formaldehyde and phenol

Test material form:

solid

Details on test material:

- Description: Light red / solid
- Storage conditions: Room temperature (15-30 °C), protected from humidity

Test animals

Species:

rat

Strain:

Wistar

Remarks:

CRL:(WI)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: ~11 weeks old
- Weight at study initiation: 204 - 236 g
- Fasting period before study: On the day 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 / group in Type II polypropylene/polycarbonate cages with Lignocel Bedding. 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. The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Water: ad libitum tap water from the municipal supply
- Acclimation period: 19, 20 or 21 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- 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
- Concentration in vehicle: test material was freshly formulated at a concentration of 200 and 30 mg/mL in the vehicle, in the Central Dispensary Unit of CiToxLAB Hungary Ltd. on the day of administration.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test material was milled before it was formulated. The formulation container was stirred continuously during administration with the objective of ensuring that the syringe was filled from a suspension.

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose level was 2000 mg/kg bw. Due to mortality, Groups 2 and 3 received a dose level of 300 mg/kg bw, respectively.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 females at 2000 mg/kg bw and 6 females at 300 mg/kg bw

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 Group 1 at 10 and 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter and on the surviving animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. 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 after. Moreover, the body weight of found dead animals was recorded at necropsy.
- Necropsy of survivors performed: yes, macroscopic examination was performed on all animals. The surviving animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthasol® 40 %). 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.

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 at the dose level of 2000 mg/kg bw (2/3) and at the dose level of 300 mg/kg bw (2/6).

Clinical signs:

other: - Treatment with the test material at the dose level of 2000 mg/kg bw caused decreased activity (3/3), hunched back (2/3), prone position (1/3), piloerection (2/3), cold to touch (1/3), incordination (3/3), increased salivation (1/3), faeces liquid (1/3),

Gross pathology:

- In the Dose group 2000 mg/kg bw, in the female 6291, beige coloured, creamy material found in the digestive content of the stomach and duodenum was regarded as potentially related to the administration of the test material. In the females 6291 and 6293, red discoloration of the non-collapsed lungs were noted at necropsy.
- In the 300 mg/kg bw Dose group, in the female 6295, red discolouration of the non-collapsed lungs considered to be typical for found dead. In the female 6311, beige coloured creamy material found in the digestive content of the stomach and duodenum was regarded as potentially related to the administration of the test material. Red discolouration of the non-collapsed lungs were also noted in this animal at necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: EU criteria: category 4, H302: harmful if swallowed

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test material was found to be between 300 and 2000 mg/kg bw in female CRL:(WI) rats.

Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 423 and EU Method B.1. Tris, under GLP conditions. The single-dose oral toxicity testing was performed using the acute toxic class method.

The test material was administered in dimethyl sulfoxide (DMSO) at concentrations of 200 and 30 mg/mL with a dosing volume of 10 mL/kg bw. Initially, three female female rats (Group 1) were treated at a dose level of 2000 mg/kg bw. The test material caused mortality in this group (2/3). Therefore a second group (Group 2) was treated at a dose level of 300 mg/kg bw. The test material caused mortality in this group (1/3). A confirmatory group (Group 3) was treated at the same dose level. One of three rats died at this dose group (Group 3), therefore no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris.

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. Clinical observations were performed on Group 1 at 10 and 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter and on the surviving animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. 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 at the dose level of 2000 mg/kg bw (2/3) and at the dose level of 300 mg/kg bw (2/6). Treatment with the test material at the dose level of 2000 mg/kg bw caused decreased activity (3/3), hunched back (2/3), prone position (1/3), piloerection (2/3), cold to touch (1/3), incoordination (3/3), increased salivation (1/3), faeces liquid (1/3), and death (2/3). Treatment with the test material at dose level 300 mg/kg bw caused decreased activity (6/6), hunched back (6/6), piloerection (1/6), faeces liquid (4/6), prone position (1/6) and death (2/6). Body weight gains of test material treated animals during the study showed no indication of a treatment-related effect at the dose level of 300 mg/kg bw.

In the Dose group 2000 mg/kg bw, in the female 6291, beige coloured, creamy material found in the digestive content of the stomach and duodenum was regarded as potentially related to the administration of the test material. In the females 6291 and 6293, red discolouration of the non-collapsed lungs were noted at necropsy. In the 300 mg/kg bw Dose group, in the female 6295, red discolouration of the non-collapsed lungs considered to be typical for found dead. In the female 6311, beige coloured creamy material found in the digestive content of the stomach and duodenum was regarded as potentially related to the administration of the test material. Red discolouration of the non-collapsed lungs was also noted in this animal at necropsy.

Under the conditions of this study, the acute oral LD50 value of the test material was found to be between 300 and 2000 mg/kg bw in female CRL:(WI) rats.