m-phenylene di(acetate)

Endpoint summary

Description of key information

Valid studies for acute oral and dermal toxicity are available.

Oral toxicity:

Six groups of 10 male young adult rats (160-180 g) were dosed at 1000, 3100, 4000, 5000, 6300 or 8200 mg/kg bw by gavage. A LD50 = 4010 mg/kg bw was found. Up to 2000 mg/kg bw no adverse effects were observed. Clinical signs at 3100 mg/kg bw and above included tremor and bloody eyes.

Dermal toxicity:

Resorcinol diacetate was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). LD50 > 2000 mg/kg bw (discriminating dose). No mortality occurred.

Inhalation toxicity:

No study available.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Six groups of 10 male young adult rats (160-180 g) were dosed at 1000, 3100, 4000, 5000, 6300 or 8200 mg/kg bw. The animals were observed for mortality, body weights, clinical signs and gross pathological changes through day 14.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Route of administration:

oral: gavage

Vehicle:

water

Doses:

1000, 3100, 4000, 5000, 6300 or 8200 mg/kg bw

No. of animals per sex per dose:

Ten male animals per dose

Control animals:

no

Statistics:

Ld50 was calculated according to Fink and Hund, Arzneim.-forsch. 15, 624 (1965).

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

4 010 mg/kg bw

Based on:

test mat.

Mortality:

0% (1000 mg/kg bw), 30% (3100 mg/kg bw), 50% (4000 mg/kg bw), 60% (5000 mg/kg bw), 90% (6300 mg/kg bw), 100% (8300 mg/kg bw).

Clinical signs:

other: Clinical signs at 3100 mg/kg bw and above included tremor and bloody eyes.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 = 4010 mg/kg bw (rat, male).

Executive summary:

Six groups of 10 male young adult rats (160-180 g) were dosed at 1000, 3100, 4000, 5000, 6300 or 8200 mg/kg bw by gavage. The animals were observed for mortality, body weights, clinical signs and gross pathological changes through day 14. A LD50 = 4010 mg/kg bw was found.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 010 mg/kg bw

Quality of whole database:

study well documented, meets generally accepted scientific principles, acceptable for assessment.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Resorcinol diacetate was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

GLP compliance:

yes

Test type:

other: singel application of 2000 mg/kg bw.

Limit test:

yes

Specific details on test material used for the study:

Identification: Resorcinol diacetate
Appearance: Brown liquid
Purity/Composition: 98.52% (GC)
Test item storage: At room temperature
CAS Number: 108-58-7
Molecular formula: C10H10O4
Molecular weight: 194.18
pH (1% in water,
indicative range): 3.60 – 3.51 (determined by Charles River Den Bosch)
Specific gravity/density: 1.18

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test System
Species: Rat, Wistar strain, Crl:WI (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC).
Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals: 5 males and 5 females (females were nulliparous and nonpregnant).
Age and body weight: Young adult animals (approx. 10-11 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean. Identification Tail mark with indelible ink.
Health inspection: At least prior to dosing. It was ensured that the animals were healthy and that the skin to be treated was intact and free from any abnormality.

Animal Husbandry
Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, at least 10 air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.
Accommodation
Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment.
Acclimatization period was at least 5 days before start of treatment under laboratory conditions. During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).
Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
Water
Free access to tap water.

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Method: Dermal application.
Clipping: One day before exposure (Day -1) an area of approximately 5x7 cm on the back of each animal was clipped.
Application: The test item was applied on an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
Frequency: Single dosage, on Day 1.
Dose level (volume): 2000 mg/kg (1.69 mL/kg) body weight. Dose volume calculated as dose level (g/kg) / density (g/mL).

Duration of exposure:

Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test item using tap water.

Doses:

Dose level (volume): 2000 mg/kg (1.69 mL/kg) body weight.

No. of animals per sex per dose:

Five male and 5 female rats/dose

Control animals:

not required

Details on study design:

Observations
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Necropsy: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

At the maximum applied dose (2000 mg/kg bw) no mortality occurred. Therefore a statistical evaluation is not necessary.

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: General erythema, scales, swelling and/or scabs were seen in the treated skin-area of the majority of animals during the observation period. Chromodacryorrhoea of the snout was noted for one female on Day 2. No further systemic clinical signs were noted.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

The dermal LD50 value of Resorcinol diacetate in Wistar rats was established to exceed 2000 mg/kg body weight.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 > 2000 mg/kg bw (discriminating dose). No mortality occurred.

Executive summary:

Resorcinol diacetate was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). LD50 > 2000 mg/kg bw (discriminating dose). No mortality occurred.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP guideline study

Justification for classification or non-classification

In the key study for oral toxicity a LD50 = 4010 mg/kg bw was found. The key study for acute dermal toxicity revealed a discriminating dose of 2000 mg/kg bw.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.