Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Study Plan, Preparation of the Test item, p. 10 deviation did not influence the quality or integrity of the present study
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,10-dichlorodecane
EC Number:
218-489-6
EC Name:
1,10-dichlorodecane
Cas Number:
2162-98-3
Molecular formula:
C10H20Cl2
IUPAC Name:
1,10-dichlorodecane
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Species/strain: WISTAR rats Crl: WI(Han)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female (non-pregnant and nulliparous)
Number of animals: 3 per step / 2 steps performed
Age at the
beginning of the study: 8-10 weeks
Body weight on the
day of administration: Step 1, animals no.: 1-3: 146 – 173g
Step 2, animals no.: 4-6: 165 – 172g
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to the German Act on Animal Welfare [9] the animals were bred for experimental purposes.
This study was performed in an AAALAC-accredited laboratory. According to German animal protection law, the study type has been reviewed and accepted by local authorities. Furthermore, the study has been subjected to Ethical Review Process and was authorised by the Bavarian animal welfare administration.
- Full barrier in an air-conditioned room
- Temperature: 22  3 °C
- Relative humidity: 55  10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
Sex: female (non-pregnant and nulliparous)
Number of animals: 3 per step / 2 steps performed
The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.
Control animals:
no

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no animal died
Clinical signs:
The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, piloerection, hunched posture, moving the bedding and half eyelid-closure. All symptoms recovered within up to 1 day post-dose.

Body weight:
Throughout the 14-day observation period, the weight gain of the animals was within the normal range of variation for this strain.
Gross pathology:
At necropsy, no macroscopic findings were observed in any animal of any step.

Any other information on results incl. tables

Step

Animal No. / Sex

Starting Dose (mg/kg bw)

Time Point

Observations

1

1 / Female

2000

0 – 120 min

nsf

120 – 180 min

Slightly reduced spontaneous activity, hunched posture, moderate piloerection,
half eyelid closure

180 min – d 2

Slightly reduced spontaneous activity, slight piloerection,
hunched posture

d 2 – d 15

nsf

2 / Female

0 – 120 min

nsf

120 min – d 2

Slightly reduced spontaneous activity, slight piloerection,
hunched posture

d 2 – d 15

nsf

3 / Female

0 – 120 min

nsf

120 min – d 2

Slightly reduced spontaneous activity, slight piloerection,
hunched posture

d 2 – d 15

nsf

Step

Animal No. / Sex

Starting Dose (mg/kg bw)

Time Point

Observations

2

4 / Female

2000

0 – 60 min

Slightly reduced spontaneous activity, hunched posture, slight piloerection

60 – 120 min

Moderately reduced spontaneous activity, hunched posture, moderate piloerection, prone position, moving the bedding

120 – 180 min

Slightly reduced spontaneous activity, hunched posture, moderate piloerection

180 min – d 2

Slightly reduced spontaneous activity, hunched posture, slight piloerection

d 2 – d 15

nsf

5 / Female

0 – 60 min

Slightly reduced spontaneous activity, hunched posture, slight piloerection

60 – 180 min

Slightly reduced spontaneous activity, hunched posture, moderate piloerection

180 min – d 2

Slightly reduced spontaneous activity, hunched posture, slight piloerection

d 2 – d 15

nsf

6 / Female

0 – 60 min

Slightly reduced spontaneous activity, hunched posture, slight piloerection

60 – 180 min

Slightly reduced spontaneous activity, hunched posture, moderate piloerection

180 min – d 2

Slightly reduced spontaneous activity, hunched posture, slight piloerection

d 2 – d 15

nsf

Step

Animal No. / Sex

Starting Dose
(mg/kg bw)

BW (g)

Body Weight Change in Comparison to Day 1 (%)

Day 1

Day 8

Day 15

Day 15

1

1 / Female

2000

173

193

210

21

2 / Female

146

168

180

23

3 / Female

173

198

212

23

2

4 / Female

168

191

205

22

5 / Female

165

186

195

18

6 / Female

172

212

214

24

Step

Animal No. / Sex

Starting Dose (mg/kg bw)

Organ

Macroscopic Findings

1

1 / Female

2000

 -

nsf

2 / Female

 -

nsf

3 / Female

 -

nsf

2

4 / Female

 -

nsf

5 / Female

 -

nsf

6 / Female

 -

nsf

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, a single oral application of the test item 1,10-Dichlorodecane to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity but not mortality. The median lethal dose of 1,10-Dichlorodecane after a single oral administration to female rats, observed over a period of 14 days is: LD50 (rat) > 2000 mg/kg bw.
Executive summary:

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was emulsified with the vehicle corn oil at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg. All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15.All animals were necropsied and examined macroscopically.

Table1:  Resultsper Step

Step

Sex / No.

Starting Dose (mg/kg bw)

Number of Animals

Number of Intercurrent Deaths

1

Female / 1 - 3

2000

3

0

2

Female / 4 - 6

2000

3

0

bw = body weight

The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, piloerection, hunched posture, moving the bedding and half eyelid-closure. All symptoms recovered within up to 1 day post-dose. Throughout the 14-day observation period, the weight gain of the animals was within the normal range of variation for this strain. At necropsy, no macroscopic findings were observed in any animal of any step.

LD50(rat):                               > 2000 mg/kg bw

Species/strain:                      WISTAR Crl: WI(Han) rats

Vehicle:                                  corn oil

Number of animals:                3 per step / 2 steps performed

Method:                                 OECD 423[4]
EC 440/2008, Method B.1 tris[5] OPPTS 870.1100[6]