Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate

Endpoint summary

Description of key information

Acute Oral toxicity

No mortality was observed in an acute oral toxicity study with the test item. The LD50 value was >5000 mg/kg bw.

Acute Dermal Toxicity

In an acute dermal toxicity study with the test item the obtained LD50 value was >2000 mg/kg bw in male and female 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:

1978-05-16 to 1978-05-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 9 weeks
- Weight at study initiation: 160 - 180 g
- Fasting period before study: No data
- Housing: Makrolon cages Typ III with dust free wood granulate, 5 animals /cage
- Diet: Altromin R 1324 ad libitum
- Water: Tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 1.5 °C
- Humidity: 60 ± 5 %
- Photoperiod: 12 hrs light/dark (artificial lighting from 7 to 19 o`clock)

Route of administration:

oral: gavage

Vehicle:

poloxamer

Remarks:

Lutrol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5 g/kg

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10 male animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Other examinations performed: Clinical signs

Key result

Sex:

male

Dose descriptor:

discriminating dose

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died at the single oral administration 5000 mg/kg/bw of Incozol 4.

Clinical signs:

other: In all animals an increased diuresis was observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity LD50 on Wistar rats of the test item Incozol 4 was determined to be >5000 mg/kg bw.

Executive summary:

The acute oral toxicity test of the test item Incozol 4 was investigated in male Wistar TNO W 74 rats. The animals were held in makrolon cages with 5 animals/cage. In total 10 male animals were used. The substance was solved in Lutrol (Poloxamer) and a single dose of 5000 mg/kg bw was conducted by gavage. Water and diet feed was given ad libitum. The animals were observed for a period of 14 days.

There were no dead animals after the observation period but in all animals an increased diuresis was observed. Therefore the LD50 of Incozol 4 was determined to be > 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

Non GLP, but scientifically well documented guideline study.

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

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

Study period:

2012-10 to 2013-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

31 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90, Hungary
- Age at study initiation: Young adult rats
- Weight at study initiation: Male: 245 - 273 g, female: 204 - 215 g
- Housing: During acclimatisation: 3 animals/sex/cage During the study: animals were housed individually
- Diet (e.g. ad libitum): ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany
- Water (e.g. ad libitum): Tap water
- Acclimation period: 19 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 8 - 12 exchanges per hour
- Photoperiod: 12 hrs dark / 12 hrs light (Artificial light, from 6 am. to 6 pm)

IN-LIFE DATES: From: 2012-09-27 To: 2012-10-31

Type of coverage:

semiocclusive

Vehicle:

other: Helianthi annui oleum raffinatum

Details on dermal exposure:

TEST SITE
- Area of exposure: back of the animals
- % coverage: 10
- Type of wrap if used: semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: body temperature water
- Time after start of exposure: 24 hours

TEST MATERIAL:
- Concentration: 400 mg/mL in vehicle (Helianthi annui oleum raffinatum)

VEHICLE
- Amount(s) applied: 5 mL/kg bw
- Lot/batch no.: 19/4

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observations: Animals were observed individually 1 h and 5 h after dosing, and once each day for 14 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.
- Inspection for signs of morbidity and mortality were made twice daily.
- Frequency of weighing: The body weight of all animals were recorded on day 0 (shortly before the treatment), on day 7 and 15 (with a precision of 1 g).
- Necropsy of survivors performed: no
- Other examinations performed: gross pathology

Statistics:

not applicable

Preliminary study:

There were no deaths in a preliminary study at 5, 50, 300 and 2000 mg/kg bw dose levels.

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occured.

Mortality:

No mortality occurred after the 24-hour dermal exposure to Incozol 4 in Crl:(WI)BR male and female rats during the study.

Clinical signs:

other: No behavioural changes or systemic toxic signs were noted during the study. Dermal irritation symptom as erythema and other sign as wound were observed on the treatment site. The slight redness (score +1) appeared in all males and was detectable between

Gross pathology:

All animals survived until the scheduled necropsy on Day 15. No macroscopic alterations due to the systemic toxic effects of the test item were found.

Other findings:

No other findings.

Interpretation of results:

GHS criteria not met

Conclusions:

In this acute dermal toxicity study with the test item Incozol 4, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.

Executive summary:

An acute dermal toxicity study was performed with test item in Crl:(WI)BR rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200.

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 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 14-day observation period. No mortality occurred after the 24-hour dermal exposure to the test item in Crl:(WI)BR male and female rats during the study. Neither male nor female animals treated with 2000 mg/kg bw of the test item showed behavioural changes and no systemic toxic signs were noted during the study. The test item caused dermal irritation symptoms as slight erythema in both sexes, between Day 1 and Day 3 in males and between Day 1 and Day 2 in females. Other dermal irritation symptom as wound was recorded in males between Day 3 and Day 6. Mean body weight development was within the normal range for male and female animals of this strain and age. The individual body weight of one female animal remained constant during the study period and no body weight gain was noted. The effect on body weight was considered to be test item related as the animal did not regain the original body weight during the study. The body weight development was undisturbed in other females. No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necroscopy. In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats. On the other hand, it is to be noted that the test item caused dermal irritation response at the site of administration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study according to guideline.

Additional information

Acute oral toxicity:

The acute oral toxicity test of the test item was investigated in male Wistar TNO W 74 rats. The animals were held in makrolon cages with 5 animals/cage. In total 10 male animals were used. The substance was solved in Lutrol (Poloxamer) and a single dose of 5000 mg/kg bw was administered by gavage. Water and diet feed was given ad libitum. The animals were observed for a period of 14 days.

There were no dead animals after the observation period but in all animals an increased diuresis was observed. Therefore, the LD50 of the test item was determined to be >5000 mg/kg bw.

Acute inhalation toxicity:

Additional testing by inhalation route is not applicable as data for oral and dermal toxicity study were available. According to the REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5.1 only information on two application routes needs to be provided, with test item administration via the most appropriate route. In addition, low inhalation exposure is expected due to the low vapour pressure of the test item.

Acute dermal toxicity:

An acute dermal toxicity study was performed with test item in Crl:(WI)BR rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200.

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 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 14-day observation period.

No mortality occurred after the 24-hour dermal exposure to the test item in Crl:(WI)BR male and female rats during the study.

Neither male nor female animals treated with 2000 mg/kg bw of the test item showed behavioural changes and no systemic toxic signs were noted during the study. The test item caused dermal irritation symptoms as slight erythema in both sexes, between Day 1 and Day 3 in males and between Day 1 and Day 2 in females. Other dermal irritation symptom as wound was recorded in males between Day 3 and Day 6.

Mean body weight development was within the normal range for male and female animals of this strain and age. The individual body weight of one female animal remained constant during the study period and no body weight gain was noted. The effect on body weight was considered to be test item related as the animal did not regain the original body weight during the study. The body weight development was undisturbed in other females.

No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy.

In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats. On the other hand, it is to be noted that the test item caused dermal irritation response at the site of administration.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item is not classified as acute oral or dermal toxic according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.