Plastic, waste, pyrolized, fractionation bottoms

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral, other

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Dose / conc.:

0 mg/kg bw/day (nominal)

Dose / conc.:

250 mg/kg bw/day (actual dose received)

Dose / conc.:

500 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

12 males per dose
12 females per dose

Observations and examinations performed and frequency:

Blood samples for hematology and clinical biochemistry analysis were collected from animals selected for repeated dose toxicity screen and animals of satellite group. The animals were placed in metabolic cages and fasted overnight before blood sampling and urine were collected and allowed access to water ad libitum. Urine samples were collected early in the morning before the blood collection. Blood samples were collected early in the working day to reduce biological variation caused by circadian rhythms. Blood samples were drawn from the retro-orbital plexus using a micro-hematocrit heparinized glass capillary tube. Plasma was used for clinical biochemistry analysis

Sacrifice and pathology:

The treated animals were euthanized by carbon dioxide asphyxiation and necropsied. Male animals from all treatment groups were sacrificed on day 43 while dams were sacrificed on day 14 postpartum. Dams which were found to be nonpregnant were sacrificed on day 25 to 33 post mating. Dead and live pups were subjected to gross examination; on postnatal day 4, one pup/litter/sex were euthanized by intraperitoneal injection of thiopentone sodium at 200 mg/kg body weight and remaining pups by carbon dioxide asphyxiation on day 13 postnatal.

Clinical signs:

no effects observed

Description (incidence and severity):

No clinical signs were observed in the control group (G1- 0 mg/kg body weight), low dose group (G2- 250 mg/kg body weight), intermediate dose group (G3-500 mg/kg body weight and in high dose group (G4-1000 mg/kg body weight) in both male and female animals.
Similarly no clinical signs were observed in the satellite control group (G1S- 0 mg/kg body weight) and in satellite high dose group (G4S-1000 mg/kg body weight) in both male and female animals.

Mortality:

no mortality observed

Description (incidence):

There were no mortalities observed in control group (0 mg/kg body weight), low dose group (250 mg/kg body weight), intermediate dose group (500 mg/kg body weight) and high dose group (1000 mg/kg body weight) animals in premating, mating, gestation and lactation period.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No toxicological significance changes in the body weight and body weight gain (%) were observed in low, intermediate and high dose group animals of both sexes when compared with control group during premating, mating, gestation, lactation and recovery period.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

No test item related changes were observed in the feed consumption of low (G2-250 mg/kg body weight), intermediate (G3-500 mg/kg body weight), high (G4-1000 mg/kg body weight) and high dose satellite (G4S-1000 mg/kg body weight) dose groups animals in both the sexes when compared with irrespective control groups in male, premating, gestation, lactation period in female and satellite groups.

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

During treatment period, significant changes in hematology parameters were observed in males (G2- 250 mg/kg body weight) and (G4- 1000 mg/kg body weight) PLT, lymph and Neut increased and decreased respectively, whereas in female (G3- 500 mg/kg body weight), increased significance observed in PLT main group animals when compared with control group. In male satellite, group (G4S- 1000 mg/kg body weight) significant increase in MCV and in female group (G4S- 1000 mg/kg body weight) Mono decreased and EOS increased were observed and no any biological significant evident.
During treatment period, significant changes in biochemistry parameters were observed in male high dose (G4- 1000 mg/kg body weight), K observed increase when compared with control (G1). In female CREA decreased in satellite high dose group (G4S- 1000 mg/kg body weight) when compared with control (G1S).
The few significant differences were observed urinal analysis parameter in (G3-500 mg/kg body weight) and (G4-1000 mg/kg body weight) of male pH was decreased are marginal and could not be attributed to test item administration.
In female during treatment period, decrease in Pro and KET increased in high dose (G4-1000 mg/kg body weight) were observed compared to control group (G1S- 0 mg/kg body weight) of animals.
The significance differences observed in hematology parameters could not be attributed to treatment due to marginal increase or decrease in individual control values

Clinical biochemistry findings:

effects observed, non-treatment-related

Description (incidence and severity):

During treatment period, significant changes in biochemistry parameters were observed in male high dose (G4- 1000 mg/kg body weight), K observed increase and in female CREA decreased in satellite high dose group (G4S- 1000 mg/kg body weight) when compared with vehicle control and could not be attributed to test item administration

Endocrine findings:

not examined

Urinalysis findings:

effects observed, non-treatment-related

Description (incidence and severity):

No treatment related significant differences were observed in all treated groups in both the sexes during treatment period.
However, in male marginal decrease in pH in high dose group (G4- 1000 mg/kg body weight) and (G4- 1000 mg/kg body weight), whereas in female decrease in Pro and increase in KET (G4-1000 mg/kg body weight) dose groups were observed compared to control group (G1- 0 mg/kg body weight).
The significance changes observed in urinary parameters are non biological significant, hence could not be attributed to treatment related adverse effect.

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

Selected animals for organ collection: No significance was recorded in absolute organ weights of male and female animals. Relative organ weight of spleen was increased in G3 female animals when compared with G1. No significance was recorded in absolute organ weights of female animals.
Remaining animals: No significance was recorded in absolute and relative organ weights of male animals. Relative organ weight of thyroid gland was increased in G3 and G4 female animals as compared to G1. Upon histopathological examination it was observed that, thyroid gland of G3 and G4 animals were within normal histological limits.
Satellite animals: Absolute and relative organ weights of liver and spleen in G4S males were significantly increased as compared to G1S males. Absolute organ weight of uterus in G4S females was significantly increased as compared to G1S females. No significance was recorded in relative organ weights of female G4S animals when compared to G1S female animals.
The above significances can be considered as incidental, as there was no dose dependent variation among the groups.

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Key result

Critical effects observed:

no

Conclusions:

The administration of TACOIL to Wistar rats by oral gavage, at dose levels of 0, 250, 500 and 1000 mg/kg/day, resulted no treatment-related clinical signs in high dose group, changes in the body weights, feed consumption in high dose group. No treatment-related effects on reproduction/ development such as mating index, fertility index, gestation length, post-natal loss, sex ratio and offspring growth and development.
Macroscopic examination revealed no test item related findings in any of the animals of 250, 500 and 1000 mg/kg as well as in high dose satellite group treated at 1000 mg/kg. No abnormality was observed attributable to test item in pups from all treatment groups.
Microscopic examination revealed no abnormality attributable to test item - TACOIL at the highest dose tested i.e. 1000 mg/kg body weight.
No Observed Effect Level (NOAEL) for Combined Repeated Dose Toxicity Study with Reproduction / Developmental Toxicity Screening Test : 1000 mg/kg body weight

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat