Santicizer 2148

Endpoint summary

Description of key information

Acute Oral LD₅₀ in Rat: >5000 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:

1990-01-03 to 1990-04-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

FIFRA: Pesticide Assessment Guidelines, Subdivision F; Hazard Evaluation: Human and Domestic Animals; Office of Pesticide Programs, U.S. Environmental Protection Agency, Office of Pesticide and Toxic Substances, Nov 1982; Sections 81-1, Acute Oral Toxicity Study

TSCA: Health Effects Test Guidelines: Office of Toxic Substances; Office of Pesticide and Toxic Substances. U.S. Environmental Protection Agency, Office of Pesticide and Toxic Substances, Aug 1982; Acute Exposure, Oral Toxicity

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

10 CD®(Sprague-Dawley derived) young adult Albino rats (approx. 9-12 weeks old at study initiation; females were nulliparous and non-pregnant) were selected for this oral toxicity study. During the equilibration period of 12 days, all animals were checked for viability twice daily. Prior to assignment to study all animals were examined to ascertain suitability for study. Animals were randomly placed in cages upon receipt and were placed on study as available at the time of study initiation. Any animals considered unsuitable because of poor health or outlying body weights were excluded.
The animals were group-housed (6/cage) during the equilibration, and individually housed during the study in suspended, stainless steel with wire mesh bottoms. The room temperature was monitored and recorded twice daily and maintained between 67-76°F. The room humidity was recorded daily and maintained without 30-70%. The room had a light cycle of 12 hours light, 12 hours dark controlled by an automatic timer.
Purina Laboratory Chow and automatic watering system were served throughout the study.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

A single dose was administrated to each animal, followed by 14 days of observation

Doses:

single oral dose of 5000 mg/Kg

No. of animals per sex per dose:

5/sex/dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Viability check twice daily, Pharmacologic and toxicologic signs observed for approximately 1, 2, and 4 hours after dosing and daily thereafter for 14 days. Body weights determined pre-fast, post-fast (just prior to dosing) and on days 7 and 14.
- Necropsy of survivors performed: yes. At termination all animals killed by carbon dioxide inhalation and examined grossly.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

All animals survived throughout the study.

Clinical signs:

other: Signs seen on the day of dosing included urinary and fecal staining, soft stool and evidence of oral discharge. One animal also had decreased food consumption on the day after dosing. All animals were free of any abnormalities from day 4 through terminati

Gross pathology:

Gross post-mortem observations were similar to those seen in control animals killed by carbon dioxide inhalation in this laboratory.

Table 2. Summary of Body Weights (g)
Animal Number	Pretest Weights		Day 7	Chg^a	Day 14	Chg^a
	Pre-fast	Post-fast
Males
4532	262	237	272	10	305	43
4533	270	243	325	55	368	98
4541	272	248	323	51	359	87
4546	266	239	310	44	354	76
4549	283	257	332	49	359	31
Females
4573	218	202	235	17	249	31
4579	222	206	227	5	231	9
4584	223	208	230	7	242	19
4589	218	199	230	12	236	18
4591	232	208	253	21	264	32

^a Change from prefasted weight (grams)

Table 3. Summary of pharmacologic and toxicologic signs^a

Observations	Interval	Day				1	2	3	4-14
		Hour	1	2	4	24
			M/F	M/F	M/F	M/F	M/F	M/F	M/F
Dry oral discharge			1/-	-	-	-	-	-	-
Urinary staining			-	-	2/1	3/3	1/-	-/1	-
Fecal staining			1/-	2/1	4/2	3/2	-	-	-
Unthrifty coat			-	-	-	2/-	5/2	2/1	-
Soft stool			1/-	1/-	2/-	-	-	-	-
Food consumption decrease			-	-	-	1/-	-	-	-

^a Number represent number of males and females (M/F), out of 5 per sex which exhibited signs one or more times during the interval

 

Table 4. Post-mortem observations – terminal necropsy (day 14)

Necropsy observations	Males					Females
	4532	4533	4541	4546	4549	4573	4579	4584	4589	4591
External
No observable abnormalities	X	X	X	X	X	X	X	X	X	X
Internal
Red foci	a	a	a	a	a	a	a	a	a	a
Discolouration	a	a	a	a	a	a	a	a	a	A
Swollen uterus								X		X

^a Changes considered due to carbon dioxide inhalation

X = observation present

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the lack of adverse treatment-related effects observed, the acute oral LD50 of XP-2563 in rats was determined to be greater than 5000 mg/Kg bw.

Executive summary:

A key Guideline EPA 81 -1 study was conducted to evaluate the oral toxicity of the test material (XP-2563) in rats. 10 young adult CD (Sprague-Dawley) derived rats received the test material as a single dose via oral gavage at 5000 mg/Kg. Pharmacologic and toxicologic signs were evaluated for at approximately 1, 2, and 4 hours after dosing and daily thereafter for 14 days. Body weights determined pre-fast, post-fast (just prior to dosing) and on days 7 and 14. At termination all animals were killed by carbon dioxide inhalation and examined grossly.

No mortality was observed through the study period and signs observed on the day of dosing included urinary and fecal staining, soft stool, and evidence of oral discharge. One animal was observed to have decreased food consumption on the day after dosing. All animals were free of any abnormalities from day 4 through termination of the study on day 14. Based on the lack of adverse treatment-related effects observed, the acute oral LD₅₀ of XP-2563 in rats was determined to be greater than 5000 mg/Kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

EPA OPPTS Guideline 81-1 acute oral toxicity study in rats.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute Oral Toxicity

A key Guideline EPA 81 -1 study was conducted to evaluate the oral toxicity of the test material (XP-2563) in rats (Bio/dynamics Inc., 1990a). 10 young adult CD (Sprague-Dawley) derived rats received the test material as a single dose via oral gavage at 5000 mg/Kg. Pharmacologic and toxicologic signs were evaluated for at approximately 1, 2, and 4 hours after dosing and daily thereafter for 14 days. Body weights determined pre-fast, post-fast (just prior to dosing) and on days 7 and 14. At termination all animals were killed by carbon dioxide inhalation and examined grossly.

No mortality was observed through the study period and signs observed on the day of dosing included urinary and fecal staining, soft stool, and evidence of oral discharge. One animal was observed to have decreased food consumption on the day after dosing. All animals were free of any abnormalities from day 4 through termination of the study on day 14.

Based on the lack of adverse treatment-related effects observed, the acute oral LD₅₀ of XP-2563 in rats was determined to be greater than 5000 mg/Kg bw.

Justification for classification or non-classification

Santicizer 2148 Plasticizer is not classified for acute lethality by the oral route of exposure under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).