Reaction products of cyclododeca-1,5,9-triene and dinitrogen monoxide, distillation overheads

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug- Oct 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001-12-17

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesanstalt für Umwelt Baden-Württemberg

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (4Z,8E)-dodeca-4,8,11-trienal and (4E,8Z)-dodeca-4,8,11-trienal

EC Number:

701-295-5

Molecular formula:

C12 H18 O

IUPAC Name:

Reaction mass of (4Z,8E)-dodeca-4,8,11-trienal and (4E,8Z)-dodeca-4,8,11-trienal

Specific details on test material used for the study:

Test material is the main constituent of the registered substance.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han) SPF

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: [yes/no] : yes
- Age at study initiation: Approx. 10 weeks
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight) 173-182 g
- Fasting period before study: At least 16 h before administration
- Housing: Single housing in fully air-conditioned rooms
- Acclimatization: At least 5 d
- Feeding: R/M maintenance, low phytoestrogen; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany), ad libitum
- Water (e.g. ad libitum): Tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 – 70%
- Air changes (per h): Approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

for 300 mg/kg bw treatment

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 15 g/100 mL
- Justification: Solution in corn oil Ph.Eur.

MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg bw for doses of 300 mg/kg bw; 2.26 mL/kg bw for doses of 2000 mg/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: By request of the sponsor

Doses:

300 mg/kg bw; 2000 mg/kg bw

No. of animals per sex per dose:

3 female rats/ dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations of clinical signs: Several times on the day of administration and at least once a week
- Frequency of weighing: Day 0, 7d, 14d
- Necropsy of survivors performed: yes

Statistics:

Calculations were performed using Microsoft Excel 2010 and checked with a calculator

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

no mortality occured

Mortality:

no mortality occured

Clinical signs:

other: Clinical signs in the second 2000 mg/kg test group: impaired general state and piloerection from hour 1 until hour 4 after administration, while dyspnea and cowering position were noted in these animals at hour 2. No clinical signs were observed after ex

Gross pathology:

There were no macroscopic pathological findings

Any other information on results incl. tables

Tab. 2: Mortality

Mortality
Dose (mg/kg bw):	2000	2000	300
Sex:	female	female	female
Administration:	1	2	1
No. of animals:	3	3	3
Mortality (animals):	No mortality	No mortality	No mortality

Tab. 3: Maximum incidence of clinical signs

Maximum incidence of systemic clinical signs
Dose (mg/kg bw):	2000
Sex:	female
Administration:	1
No. of animals:	3
Animal No.:	R300	R301	R302
Abnormalities:	-	-	-
Dose (mg/kg bw):	2000
Sex:	female
Administration:	2
No. of animals:	3
Animal No.:	R312	R313	R314
Abnormalities:
Impaired general state:	h1-h4	h1-h4	h1-h4
Piloerection:	h1-h4	h1-h4	h1-h4
Dyspnea:	h2	h2	h2
Cowering position:	h2	h2	h2
Dose (mg/kg bw):	300
Sex:	female
Administration:	1
No. of animals:	3
Animal No.:	R281	R282	R283
Abnormalities:	-	-	-

* h - hour

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg bw in female rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, doses of 2000 and 300 mg/kg bw of the test item (undiluted or preparations in corn oil Ph.Eur.) were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 6 females and 300 mg/kg bw in 3 females).

All animals gained weight in a normal range throughout the study period.

There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (9 females).

Clinical signs (impaired general state and piloerection, dyspnea and cowering position) were observed in the second 2000 mg/kg test group.

The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw.