Poly(oxy-1,2-ethanediyl), α,α'-(iminodi-2,1-ethanediyl)bis[.omega.-hydroxy-, N-[3-(C10-16-alkyloxy)propyl] derivs., di-Et sulfate-quaternized

Endpoint summary

Description of key information

The median lethal dose of the test item after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): 500 mg/ kg bw.

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:

2017

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)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Name: Poly(oxy-1,2-ethanediyl), .alpha.,.alpha.'-(iminodi-2,1-ethanediyl)bis[.omega.-hydroxy-, N-[3-(C10-16-alkyloxy)propyl] derivs., di-Et sulfate-quaternized
Product Description: C10-16-alkyletherpropylamine, ethoxylated, DES Quat
CAS No.: 70983-58-3
Physical state: yellowish to amber viscous liquid at 20 °C
Batch No.: PFS-755-173
Re-certification date of batch: 19 April 2018
Purity: 100 % (UVCB)
Color, Gardner 8.8
pH, 5% in water 5.76
Acid Value , mg KOH/g 20.1
Moisture, % 0.127
Total Amine, mg/g 11.18
Viscosity,cps, #4@60,25C 3280
Appearance @25C pass
Stability: stable under test conditions
Storage condition of test material: Room temperature, protected from light

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Test System

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
Age at the beginning of the study: 8-12 weeks
Body weight on the day of administration:
step 1, animals no. 1-3: 195 - 217 g
step 2, animals no. 4-6: 180 - 220 g
step 3: animasl no. 7-9: 173 – 185 g

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.

Housing and Feeding Conditions

- 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

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test item was administered at a single dose by gavage using a feeding tube. The test item was administered undiluted.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

test mat. (total fraction)

Mortality:

The test item showed mortality and other acute oral toxicity characteristics after a single dose administration at a dosage of 2000 mg/kg body weight. With a dosage of 300 mg/kg body weight the test item showed slight signs of toxicity but no mortality.

Clinical signs:

other: The test item showed mortality and other acute oral toxicity characteristics after a single dose administration at a dosage of 2000 mg/kg body weight. With a dosage of 300 mg/kg body weight the test item showed slight signs of toxicity but no mortality.

Gross pathology:

The necropsy of the animals dosed with 2000 mg/kg bw revealed a dark discoloured liver. At necropsy the livers were already autolytic.
The necropsy of the animals dosed with 300 mg / kg bw revealed no specific findings.

Results

The test item showed mortality and other acute oral toxicity characteristics after a single dose administration at a dosage of 2000 mg/kg body weight. With a dosage of 300 mg/kg body weight the test item showed slight signs of toxicity but no mortality.

Table 1: Clinical Signs - Individual Data

Step	Starting dose (mg/kg bw)	Animal No. / Sex	Timepoint	Observation
1	2000	1 / Female	0 - 120 min	nsf
1	2000	1 / Female	120 - 180 min	Slightly reduced spontaneous activity, hunched posture, slight piloerection, half eyelid closure
1	2000	1 / Female	180 - 240 min	Moderately reduced Spontaneous activity, hunched posture, moderate piloerection , half eyelid closure, sunken flanks
1	2000	1 / Female	240 min - d 2	Moderately reduced spontaneous activity, hunched posture, moderate piloerection, eyes closed, sunken flanks, slight diarrhoea
1	2000	1 / Female	d 2	found dead
1	2000	2 / Female	0 - 120 min	nsf
1	2000	2 / Female	120 - 180 min	Slightly reduced spontaneous activity, hunched posture, slight piloerection, half eyelid closure
1	2000	2 / Female	180 - 240 min	Moderately reduced spontaneous activity, hunched posture, moderate piloerection , half eyelid closure, sunken flanks
1	2000	2 / Female	240 min - d 2	Moderately reduced spontaneous activity, hunched posture, moderate piloerection, eyes closed, Sunken flanks
1	2000	2 / Female	d 2	found dead
1	2000	3 / Female	0 - 120 min	nsf
1	2000	3 / Female	120 - 180 min	Moderately reduced spontaneous activity, hunched posture, moderate piloerection, half eyelid closure, sunken flanks
1	2000	3 / Female	180 - 240 min	Moderately reduced spontaneous activity, hunched posture, moderate piloerection, eyes closed, sunken flanks
1	2000	3 / Female	240 min - d 2	found dead

Table 2: Clinical Signs - Individual Data

Step	Starting dose (mg/kg bw)	Animal No.	Timepoint	Observation
2	300	4 / Female	0 - 180 min	nsf
2	300	4 / Female	180 - 240 min	Hunched posture, moderate piloerection
2	300	4 / Female	240 min - 2 d	Hunched posture, moderate piloerection, half eyelid closure
2	300	4 / Female	d 2 - d 15	nsf
2	300	5 / Female	0 - 180 min	Hunched posture, moderate piloerection
2	300	5 / Female	180 - 240 min	Hunched posture, moderate piloerection, half eyelid closure
2	300	5 / Female	240 min - 2 d	nsf
2	300	5 / Female	d 2 - d 15	nsf
2	300	6 / Female	0 - 180 min	nsf
2	300	6 / Female	180 - 240 min	Hunched posture, moderate piloerection
2	300	6 / Female	240 min - 2 d	Hunched posture, moderate piloerection, half eyelid closure
2	300	6 / Female	d 2 - d 15	nsf
3	300	7 / Female	0 min – d 15	nsf
3	300	8 / Female	0 min – d 15	nsf
3	300	9 / Female	0 min – d 15	nsf

Based on these results and according to the acute toxic class method regime no further testing was required. Therefore, according to OECD Guideline 423, a sufficient estimation of the acute oral toxicity of the test item is provided.

 

Body Weight Development

None of the animals showed weight loss during the observation period.

Table 3: Absolute Body Weights in g and Body Weight Gain in %

Step	Animal No. / Sex	Starting material (mg/kg bw)	BW (g)			Body weight in comparison to day 1 (%)
			Day 1	Day 8	Day 15	15
Step 1	1 / Female	2000	197	found dead on day 2
Step 1	2 / Female	2000	217	found dead on day 2
Step 1	3 / Female	2000	195	found dead on day 2
Step 2	4 / Female	300	214	237	240	12
Step 2	5 / Female	300	220	246	248	13
Step 2	6 / Female	300	180	194	203	13
Step 3	7 / Female	300	184	202	220	20
Step 3	8 / Female	300	173	180	200	16
Step 3	9 / Female	300	185	215	217	17

Pathology

The necropsy of the animals dosed with 2000 mg/kg bw revealed a dark discoloured liver. At necropsy the livers were already autolytic. The necropsy of the animals dosed with 300 mg / kg bw revealed no specific findings.

Table 4: Findings of the Necropsy - Individual Data

Step	Animal No. / Sex	Starting Dose (mg/kg bw)	Organ	Macroscopic Findings
Step 1	1 / Female	2000	Liver	Discoloured, dark*
Step 1	2 / Female	2000	Liver	Discoloured, dark*
Step 1	3 / Female	2000	Liver	Discoloured, dark*
Step 2	4 / Female	300	-	nsf
Step 2	5 / Female	300	-	nsf
Step 2	6 / Female	300	-	nsf
Step 3	7 / Female	300	-	nsf
Step 3	8 / Female	300	-	nsf
Step 3	9 / Female	300	-	nsf

bw = body weight; nsf = no specific findings; * = autolytic

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The median lethal dose of the test item after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): 500 mg/ kg bw.

Executive summary:

In a Klimisch 1 OECD 423 GLP study a single oral application of the test item to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity and mortality.

Under the conditions of the present study, a single oral application of the test item to rats at a dose of 300 mg/kg body weight was associated with slight signs of toxicity but not with mortality.

The median lethal dose of the test item after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): 500 mg/ kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

500 mg/kg bw

Quality of whole database:

OECD 423 guideline GLP study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available