Reaction mass of lauric acid, compound with morpholine (1:1) and 2-ethylhexyl dihydrogen phosphate, compound with morpholine (1:2) and bis(2-ethylhexyl) hydrogen phosphate, compound with morpholine (1:1)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-03-02 to 2016-04-11

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of lauric acid, compound with morpholine (1:1) and 2-ethylhexyl dihydrogen phosphate, compound with morpholine (1:2) and bis(2-ethylhexyl) hydrogen phosphate, compound with morpholine (1:1)

EC Number:

915-372-8

Molecular formula:

not applicable (multi-const.substance)

IUPAC Name:

Reaction mass of lauric acid, compound with morpholine (1:1) and 2-ethylhexyl dihydrogen phosphate, compound with morpholine (1:2) and bis(2-ethylhexyl) hydrogen phosphate, compound with morpholine (1:1)

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult rats
- Weight at study initiation: 200-219 g
- Fasting period before study: not applicable
- Housing: During acclimatisation: 3 animals/sex/cage During the study: animals were housed individually. Cage type: Type II polypropylene/polycarbonate; rat type cages with a solid floor, stainless steel wire covers and self-feeding baskets.
- Diet: The animals received ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum. The food was periodically analysed and was considered free from any contaminants that could have affected the purpose or integrity of the study. Copies of the relevant Certificates of Analysis are maintained in Toxi-Coop Zrt.’s archive.
- Water: Animals received tap water from watering bottles ad libitum. The drinking water was periodically analysed and was considered free from any contaminates that could have affected the purpose or integrity of the study. Copies of the relevant Certificates of Analysis are maintained in Toxi-Coop Zrt.’s archive.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: Above 10 air exchanges/hour by central air-condition system.
- Photoperiod: Artificial light, from 6 am. to 6 pm.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: approx. 10 % of total body surface area, at the back
- % coverage: at least 10% area of the total body surface
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats. These gauzes were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was wrapped with semi-occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period, residual test item was removed, using body temperature water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000, 300, 50, 5 mg/kg bw
- Concentrations: 400, 60, 10, 1 mg/ml
- Constant volume or concentration used: yes. 5 mL/kg bw of respective concentration
- For solids, paste formed: yes

VEHICLE
- Lot/batch no.: 1511-5526
- Purity: Aqua purificata
- Date of expiration: 26 May 2016
- Supplier: Parma Produkt Kft.

Duration of exposure:

24 h

Doses:

2000, 300, 50, 5 mg/kg bw

No. of animals per sex per dose:

2

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day. Animals were observed individually 1 h and 5 h after dosing, and once each day for 7 days thereafter. Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The body weights were recorded on day 0 (shortly before the treatment) and on Day 7 (with a precision of 1 g).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred after the 24-hour dermal exposure to Madurit TM 3750 in HsdHan:WIST female rats during the preliminary study.

Clinical signs:

other: No systemic toxic signs were noted during the study in all doses. In group 1 treated with 2000 mg/kg bw dermal corrosive symptoms as erythema and other signs as necrosis, desquamation and wound were observed in both animals on the treatment site. Severe r

Gross pathology:

All animals survived until the scheduled necropsy on Day 7. In group 1 (2000 mg/kg bw) external macroscopic changes as necrosis, desquamation and wound were observed on the treatment site in both animals (No.: 1109, 1125). In group 2 (300 mg/kg bw) external macroscopic changes as dry and desquamated skin were observed on the treatment site in both animals (No.: 1122, 1123). Internal necropsy finding as pale liver was found in animal No.: 1123. Severe hydrometra was recorded in animal No.: 1122. In group 3 (50 mg/kg bw) internal macroscopic change as pale liver was observed in animal No.: 1121. In group 4 (5 mg/kg bw) severe hydrometra was observed in animal No.: 1124. No macroscopic alterations due to the systemic toxic effects of the test item were found.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In this preliminary acute dermal toxicity study with the test item Madurit TM 3750, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in female HsdHan:WIST rats. According to Regulation (EC) No 1272/2008 and UN GHS, the test item has not been classified into any category. On the other hand, it is to be noted that the test item caused dermal corrosion/irritation response on the site of administration.

Executive summary:

An acute dermal toxicity study was performed with the test item in HsdHan:WIST female rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200. Only a preliminary study was carried out because of severe skin corrosive effect of the test item observed in the 2000 mg/kg bw dose group. Altogether four groups (n=2 animals) was exposed to the test item at 2000, 300, 50 and 5 mg/kg bw by dermal route. The test item was applied in diluted form and left in contact with the skin for 24 hours, followed by a 7-day observation period. The vehicle was distilled water. The results of the preliminary study were summarised as follows: No mortality occurred after the 24-hour dermal exposure to the test item in all groups during the study. No systemic toxic signs were noted during the study in all doses. The test item caused local dermal corrosion/irritation symptoms on the treatment site. Severe erythema, necrosis, desquamation and wound occurred in the 2000 mg/kg bw dose group between Day 1 and Day 7. Very slight to well defined redness, dry skin and desquamation were observed in the300 mg/kg bw dose group between Day 1 and Day 7. Well defined redness was observed in the 50 mg/kg bw dose group between Day 1 and Day 2. No local dermal symptoms were found in the 5 mg/kg bw dose. Mean body weight development was within the normal range for all animals of this strain and age. It is to be noted that a backwardness of body weight gain was observable in the 2000 mg/kg bw dose compared to other groups. It is explicable with the marked distress and pain due to corrosive effect of test item. No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy. In this preliminary acute dermal toxicity study with the test item Madurit TM 3750, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in female HsdHan:WIST rats. According to Regulation (EC) No 1272/2008 and UN GHS, the test item has not been classified into any category. On the other hand, it is to be noted that the test item caused dermal corrosion/irritation response on the site of administration.