Reaction product of Fatty acids, C18-unstaturated, dimer with 4,7,10-trioxa-1,13-tridecane-diamine

Endpoint summary

Description of key information

Two acute lethality studies have been conducted on MTDID 18990.

Acute Oral Lethality: LD50 greater than 2000 mg/kg when tested according to OECD 423.

Acute Dermal Lethality: LD50 greater than 2000 mg/kg when tested according to OECD 402.

The acute oral lethality potential of MTDID 18990 was evaluated in Wistar rats. The study was conducted according to OECD 423 in compliance with OECD GLP. Rats (6 females) received 2000 mg/kg MTDID 18990 “neat” as a liquid via oral gavage. No mortality occurred. Clinical observations of toxicity included hunched posture (6/6 rats on Days 1 and 2 and one animal on Day 3), uncoordinatedmovements (3/6 females at 2 and 4 hours post-dose; only the second set of dosed animals), and piloerection (6/6 rats through 4-hours post-dose). The mean body weight gain shown by the animals over the study in-life period was considered to be similar to that expected for normal untreated animals of the same ageand strain. No abnormalities were found at macroscopic post mortem examination of the animals. The rat oral LD50 is >2000 mg/kg with significant signs of clinical toxicity (i.e., hunched posture and uncoordinated movements).  Based on the results of the study, the acute oral LD50 of MTDID 18990 is greater than 2,000.

The acute dermal lethality potential of MTDID 19880 was evaluated in Wistar rats.  The study was conducted according to OECD 402, in compliance with OECD GLP.  Rats (3 female) received a single dermal application of 2000 mg/kg MTDID 18990; the test article was applied to clipped skin and held in contact with the body with surgical gauze covered with a Coban elastic bandage for 24 hours. All three rats survived the exposure period and subsequent 14-day recovery period. Focal erythema, scales, scabs and/or necrosis were noted at the treatment sites of the animals, but those were not considered indicative of systemic toxicity. No clinical signs of adverse systemic toxicity were observed. The rat dermal LD50 is>2000 mg/kg of body weight in rats.

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

Study period:

2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: 3M Company, Lot 4293484
- Expiration date of the lot/batch: 31 January, 2021
- Purity test date: 19 December, 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature protected from light.
- Stability under storage conditions: No data
- Stability under test conditions: No data
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium:
- Reactivity of the test substance with the solvent/vehicle /test medium (if applicable):

TREATMENT OF TEST MATERIAL PRIOR TO TESTING : Test article dosed neat

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Approximately 12 weeks old.
- Weight at study initiation: 163-209 grams
- Fasting period before study: 20 hours.
- Housing: On arrival and following assignment to the study, animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. The room in which the animals were kept was documented in the study records. Animals were separated during designated procedures/activities. Each cage was clearly labeled.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles
- Acclimation period: At least 5 days
- Microbiological status when known : No data
- Method of randomisation in assigning animals to test and control groups : Animals were assigned to the study at the discretion of the coordinating bio technician according to body weights, with all animals within ± 20% of the sex mean. Animals in poor health or at extremes of body weight range were not assigned to the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 38-51
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28 March, 2019 To: 16 April, 2019

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: None, dosed neat.

MAXIMUM DOSE VOLUME APPLIED: No data

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The test article is not expected to be acutely lethal via ingestion so the test article was administered at 2000 mg/kg to 3 female rats. As there were not adverse clinical signs or mortality, a group of 3 additional female rats were dosed at 2000 mg/kg.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings. Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored. Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: Yes, all animals were sacrificed by oxygen/carbon dioxide procedure at the end of the observation period. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Preliminary study:

None

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the study.

Clinical signs:

other: Hunched posture, uncoordinated movements and/or piloerection were noted between Days 1 and 3.

Gross pathology:

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

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The oral LD50 value of MTDID 18990 in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The acute oral lethality potential of MTDID 18990 was evaluated in Wistar rats. The study was conducted according to OECD 423 in compliance with OECD GLP. Rats (6 females) received 2000 mg/kg MTDID 18990 “neat” as a liquid via oral gavage. No mortality occurred. Clinical observations of toxicity included hunched posture (6/6 rats on Days 1 and 2 and one animal on Day 3), uncoordinatedmovements (3/6 females at 2 and 4 hours post-dose; only the second set of dosed animals), and piloerection (6/6 rats through 4-hours post-dose). The mean body weight gain shown by the animals over the study in-life period was considered to be similar to that expected for normal untreated animals of the same ageand strain. No abnormalities were found at macroscopic post mortem examination of the animals. The rat oral LD50 is >2000 mg/kg with significant signs of clinical toxicity (i.e., hunched posture and uncoordinated movements).  Based on the results of the study, the acute oral LD50 of MTDID 18990 is greater than 2,000.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
As inhalation is an unlikely route of exposure, an acute dermal lethality study was conducted as dermal exposure is a far more likely route of exposure.

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

Study period:

2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

2017

Deviations:

no

Remarks:

No deviations ocurred that negatively impacted the integrity of the study.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material:
3M Company, Lot 4293484
- Expiration date of the lot/batch:
31 January 2021
- Purity test date:
10 November, 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
At room temperature protected from light
- Stability under storage conditions:
No data
- Stability under test conditions:
No data
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium:
The test article was dosed neat.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
: The test article was dosed neat.

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 9-12 weeks old
- Weight at study initiation: 184-212
- Housing: On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) and following assignment to the study, an imals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. The room in which the animals were kept was documented in the study records. Animals were separated during designated procedures/activities. Each cage was clearly labeled.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24 (mean 21)
- Humidity (%): 40-64
- Air changes (per hr): 10 or greater
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 06 May, 2019 To: 17 June, 2019

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5x7 cm on the back of each rat
- % coverage: Approximately 10%
- Type of wrap if used: The test item was held in contact with the skin with a dressing, consisting of
a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage. A piece of
Micropore tape was additionally used for fixation of the bandages.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, 24 hours after the start of exposure with water.
- Time after start of exposure: 24 hours.
OBSERVATION TIME POINTS : The skin reactions were assessed at approximately 24, 48 and 72
hours after the removal of the dressing and test item.
SCORING SYSTEM:
- Method of calculation: Draize

Duration of exposure:

24 hours

Doses:

- 2000 mg/kg bw

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings. Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals during and for the first hour after dosing. Animals were weighed individually on Days 1 (predose), 8 and 15.
- Necropsy of survivors performed: yes
- Clinical signs including body weight : yes
- Other examinations performed: clinical signs, body weight, gross pathology, irritation.

The skin reactions were assessed at approximately 24, 48 and 72 hours after the removal of the dressing and test item. Adjacent areas of untreated skin of each animal served as controls.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Preliminary study:

None.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred at 2000 mg/kg.

Clinical signs:

other: No clinical signs of systemic toxicity were noted.

Gross pathology:

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

Other findings:

Focal erythema, scales, scabs and/or necrosis was noted at the treated skin of the animals throughout the observation period. These local effects were considered not indicative of systemic toxicity.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 value of MTDID 18990 in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Executive summary:

The acute dermal lethality potential of MTDID 18990 was evaluated in Wistar rats.  The study was conducted according to OECD 402, in compliance with OECD GLP.  Rats (3 female) received a single dermal application of 2000 mg/kg MTDID 18990; the test article was applied to clipped skin and held in contact with the body with surgical gauze covered with a Coban elastic bandage for 24 hours. All three rats survived the exposure period and subsequent 14-day recovery period. Focal erythema, scales, scabs and/or necrosis were noted at the treatment sites of the animals, but those were not considered indicative of systemic toxicity. No clinical signs of adverse systemic toxicity were observed. The rat dermal LD50 is>2000 mg/kg of body weight in rats.

Justification for classification or non-classification

MTDID 18990 is not classified for acute oral or dermal lethality. Based on the uncoordinated movements observed in the acute oral lethality study, a classification of STOT SE3 (H336) was assigned.